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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated cellular responses in a rabbit to i.v. administration of five established chemotactic factors (leukotriene B4 (LTB4), platelet-activating factor (PAF), C5a, N-Formyl-Met-Leu-Phe (F-MLF), and IL-8), and each exerted a characteristic effect on circulating white blood cell levels. All five factors induced a rapid and transient leukopenia. The blood was nearly devoid of circulating neutrophils 5 min after administration of each chemotactic factor. Other leukocytes were also variably depleted during the leukopenic phase, including eosinophils, basophils, monocytes, and lymphocytes. The lymphocyte numbers remained significantly depressed (approximately 30%) for as long as 3 h after administration of PAF or f-MLF. Each chemotactic factor produced a marked neutrophilia (i.e., 250-400% of baseline levels) after the initial leukopenia. Eosinophil numbers were elevated along with the neutrophil response in the C5a- and LTB4-treated animals. Basophil levels were significantly elevated only in LTB4-treated animals. The cellular response to PAF, f-MLF, and IL-8 appeared to be specific for the neutrophils. The kinetic profiles of the neutrophilia induced by PAF (10 micrograms/kg) or f-MLF (2.5 micrograms/kg) were similar, with maximal responses occurring 3 to 4 h after administration. In contrast, LTB4 (10 micrograms/kg), IL-8 (2.5 micrograms/kg), and C5a (5 micrograms/kg) induced a more rapid neutrophilia, with peak responses occurring 1 to 1.5 h after injection, and remaining elevated for 3 to 4 h. In all animals the neutrophilia was accompanied by a relative increase in the number of nonsegmented neutrophils (bands), suggesting that a major component of leukocytosis is caused by the release of bone marrow reserves. Phenidone (10 mg/kg), a dual cyclooxygenase/5-lipoxygenase inhibitor, affected neither the neutropenia nor the neutrophilia induced by C5a, f-MLF, or PAF. The protein synthesis inhibitor actinomycin D also failed to suppress neutrophil responses induced by either C5a or PAF. These results suggest that leukocytosis is a common response induced by all neutrophil chemotactic factors. Leukocytosis appears to be a direct result of the dynamic adaptive response of neutrophils to chemotactic factor stimulation without involvement of a secondary mediator system.
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PMID:Neutrophil chemotactic factors promote leukocytosis. A common mechanism for cellular recruitment from bone marrow. 131 Jul 8

Connective tissue activating peptide-III (CTAP-III) is a component of platelet alpha-granules which elicits a series of responses in connective tissue cells referred to as activation, including increased glucose consumption and mitogenesis and increased secretion of hyaluronic acid and glycosaminoglycans. As anticipated by a requirement for glucose or glucose precursors in the activation process, an early event following CTAP-III activation of connective tissue cells is an increase in glucose transport. The present study investigates the molecular basis for this increase in glucose transport. Murine 3T3-F442A fibroblasts were found to respond to CTAP-III in a manner similar to human connective tissue cells (synovial cells, chondrocytes, skin fibroblasts). CTAP-III increases the rate of glucose transport to similar extents at 4 and 24 h, and at physiologic (micrograms/ml) concentrations of CTAP-III. A proteolytic cleavage product of recombinant CTAP-III (rCTAP-III-Leu-21 (des-1-15)), also known as neutrophil-activating peptide-2 (NAP-2), was found to be equally effective as CTAP-III, whereas NAP-1/interleukin-8, another member of the CTAP-III super-family, was ineffective in stimulating glucose transport. This contrasts with neutrophil chemotaxis, in which CTAP-III (des-1-15)/NAP-2 acts similarly to NAP-1/interleukin 8 while CTAP-III is ineffective. CTAP-III appears to elicit a different type of glucose transport response than many other growth factors in that its response is sustained (greater than or equal to 24 h) rather than transient (peak approximately 4 h) in confluent as well as in subconfluent cells. Western blot analysis using antibodies to the GLUT-1 glucose transporter revealed an increased level of GLUT-1 protein in response to CTAP-III isoforms that corresponded in magnitude (on a percentage basis) to the increased level of glucose transport. The increased levels of GLUT-1 protein in response to CTAP-III and rCTAP-III-Leu-21 (des-1-15)/NAP-2 were accompanied by an increase in levels of GLUT-1 mRNA of a magnitude sufficient to account for observed increased levels of GLUT-1. These results are consistent with CTAP-III isoforms stimulating glucose transport in connective tissue cells by increasing levels of GLUT-1 mRNA and is one of the few known instances in which increases in levels of GLUT-1 mRNA and protein are sufficient to account for observed increases in glucose transport. They also provide further evidence that CTAP-III (des-1-15)/NAP-2 binds to more than one type of receptor and that CTAP-III acts in a manner different than other well characterized growth factors (e.g. platelet-derived growth factor, transforming growth factor-beta) in that it causes a sustained (greater than or equal to 24 h) elevation in glucose transport in confluent as well as subconfluent cells.
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PMID:Regulation of glucose transporters by connective tissue activating peptide-III isoforms. 152 75

Human neutrophils possess a superoxide (O2-)-forming NADPH oxidase which is activated by the chemoattractants, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), complement C5a, platelet-activating factor and leukotriene B4. We studied the roles of cAMP and cGMP in the regulation of O2- formation using the cell-permeant analogues of cyclic nucleotides, N6,2'-O-dibutyryl adenosine 3':5'-cyclic monophosphate (Bt2cAMP) and N2,2'-O-dibutyryl guanosine 3':5'-cyclic monophosphate (Bt2cGMP). Bt2cAMP inhibited O2- formation induced by these chemoattractants to similar extents. Bt2cGMP as low as 10 mumol/l significantly inhibited O2- formation induced by fMet-Leu-Phe at a submaximally effective concentration (50 nmol/l), and Bt2cGMP was more effective in diminishing O2- formation than Bt2cAMP. In contrast, Bt2cGMP did not affect O2- formation induced by fMet-Leu-Phe at a maximally effective concentration (1 mumol/l). Bt2cGMP (0.1 and 1 mmol/l) enhanced O2- formation induced by 0.1 mumol/1 C5a by 23% and 49%, respectively, and Bt2cGMP antagonized inhibition of O2- formation caused by Bt2cAMP. Bt2cGMP inhibited platelet-activating factor-induced O2- formation to a lesser extent than Bt2cAMP and had no effect on that induced by leukotriene B4. Bt2cAMP and Bt2cGMP had no effect on O2- formation induced by NAF, gamma-hexachlorocyclohexane, phorbol myristate acetate, A 23187 and arachidonic acid. Our data suggest that: 1. Bt2cAMP generally inhibits chemoattractant-stimulated O2- formation. 2. Bt2cGMP inhibits fMet-Leu-Phe- and platelet-activating factor-stimulated O2- formation but potentiates C5a-induced O2- formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential inhibition and potentiation of chemoattractant-induced superoxide formation in human neutrophils by the cell-permeant analogue of cyclic GMP, N2,2'-O-dibutyryl guanosine 3':5'-cyclic monophosphate. 164 10

We have shown previously that interleukin 8 (IL-8) induces histamine and leukotriene release in human basophils exposed to interleukin 3 (IL-3). We now found that pretreatment with low concentrations of IL-8 selectively inhibits this response. Inhibition was significant at 0.01 nM IL-8 and virtually complete at 1 nM, which is about 100-fold lower than the concentration required for induction of mediator release. IL-8 dependent responses were also inhibited, albeit to a lesser extent, by preincubation with neutrophil-activating peptide 2 (NAP-2), but not with connective tissue-activating peptide III (CTAP-III) or platelet factor 4 (PF4). Release induced by C5a, fMet-Leu-Phe, or anti-IgE antibody, by contrast, was not affected.
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PMID:Interleukin 8-inhibitor and inducer of histamine and leukotriene release in human basophils. 171 99

Plasmin mainly cleaved the Arg5-Ser6 bond of Arg-Val-Leu-Pro-Arg-interleukin-8 (AVLPR-IL-8) produced by human dermal fibroblasts, which resulted in the conversion of AVLPR-IL-8 to IL-8 and the inactive pentapeptide, though a minor cleavage of AVLPR-IL-8 by plasmin at Lys8-Glu9 bond occurred.
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PMID:Generation of interleukin-8 by plasmin from AVLPR-interleukin-8, the human fibroblast-derived neutrophil chemotactic factor. 182 38

Interleukin-8 (IL-8) is a member of a family of pro-inflammatory cytokines. Although the best characterized activities of IL-8 include the chemoattraction and activation of neutrophils, other members of this family have a wide range of specific actions including the chemotaxis and activation of monocytes, the selective chemotaxis of memory T cells, the inhibition of hematopoietic stem cell proliferation, and the induction of neutrophil infiltration in vivo. A complementary DNA encoding the IL-8 receptor from human neutrophils has now been isolated. The amino acid sequence shows that the receptor is a member of the superfamily of receptors that couple to guanine nucleotide binding proteins (G proteins). The sequence is 29% identical to that of receptors for the other neutrophil chemoattractants, fMet-Leu-Phe and C5a. Mammalian cells transfected with the IL-8 receptor cDNA clone bind IL-8 with high affinity and respond specifically to IL-8 by transiently mobilizing calcium. The IL-8 receptor may be part of a subfamily of related G protein-coupled receptors that transduce signals for the IL-8 family of pro-inflammatory cytokines.
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PMID:Structure and functional expression of a human interleukin-8 receptor. 184 Jul 1

Recently a rabbit cDNA (F3R) was characterized as binding and causing calcium mobilization induced by the formyl-methionine-leucine-phenylalanine peptide (fMLP). In the study reported here, cloned DNAs were isolated from rabbit genomic DNA by PCR based on the sequence of F3R. The cloned DNAs have several differences in the DNA sequence compared to the reported F3R sequence that alter the predicted protein sequence. COS-7 cells transfected with these clones in a mammalian expression vector bind human IL-8 with high affinity, but do not bind fMLP. We therefore believe that the cDNAs isolated encode the rabbit IL-8 receptor.
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PMID:Molecular characterization of the interleukin-8 receptor. 189

During the chemotactic migration of human neutrophilic granulocytes towards the chemotactic factors f-Met-Leu-Phe, C5a, leukotriene B4 (LTB4), monocyte-derived chemotaxin (MOC/IL-8) and platelet-activating factor (PAF) in Boyden chambers, the production of superoxide anion and hydrogen peroxide was measured by superoxide dismutase-inhibitable cytochrome C reduction and oxidation of p-OH-phenylacetic acid, respectively. With the exception of 10(-6) M PAF, none of the factors at optimal chemotactic concentrations induced the production of O2- or H2O2 in amounts significantly different from neutrophilic granulocytes migrating at random. At 20-50 times the optimal chemotactic concentration some O2- and H2O2 production was observed with f-Met-Leu-Phe, C5a and LTB4, but not with MOC/IL-8. Superoxide dismutase, catalase or a combination of the two added to both compartments of the Boyden chambers did not affect the random or chemotactic migration towards any of the chemotactic factors. The results suggest that chemotactic migration and the production of reactive oxygen metabolites by human neutrophilic granulocytes are unrelated events.
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PMID:Production of superoxide anion and hydrogen peroxide by human neutrophilic granulocytes during chemotactic migration towards f-Met-Leu-Phe, C5a, leukotriene B4, monocyte-derived chemotaxin/IL-8 and platelet-activating factor. 196 31

Monocyte-derived neutrophil chemotactic factor/interleukin-8 (MDNCF/IL-8) is an 8,000-dalton protein produced by monocytes which exhibits activity as a chemoattractant for neutrophils with maximal activity achieved at a concentration of 50 ng/ml. This polypeptide has been iodinated by chloramine-T methodology (350 Ci/mM), and specific receptors for MDNCF/IL-8 have been detected on human neutrophils, U937 cells, THP-1 cells, and dimethyl sulfoxide-differentiated HL-60 cells. The binding of MDNCF/IL-8 to human neutrophils is not inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, insulin, or epidermal growth factor. In addition, chemoattractants such as C5a, fMet-Leu-Phe, leukotriene B4, and platelet-activating factor fail to inhibit binding, suggesting that MDNCF/IL-8 utilizes a unique receptor. The receptor for MDNCF/IL-8 is apparently glycosylated since ligand binding is inhibited by the presence of wheat germ agglutinin, a lectin with a binding specificity for N-acetylglucosamine and neuraminic acid. Steady state binding experiments indicate Kd values of 4 and 0.5 nM and receptor numbers of 75,000 and 7,400 for human neutrophils and differentiated HL-60 cells, respectively. 125I-MDNCF/IL-8 bound to human neutrophils is rapidly internalized and subsequently released from cells as trichloroacetic acid-soluble radioactivity. Affinity labeling experiments suggest that the human neutrophil MDNCF/IL-8 receptor exhibits a mass of approximately 58,000 daltons.
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PMID:Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8. 218 41

Microheterogeneity of connective tissue activation peptide III (CTAP-III) was revealed by preparative and analytical isoelectric focusing. Proteolytic activities in human platelet preparations resulted in four cleavage products of platelet-derived CTAP-III. Three isoforms (CTAP-III des 1-13, des 1-14, and des 1-15/NAP-2) stimulate [14C]glycosaminoglycan synthesis; two isoforms also promote [3H]DNA synthesis in human fibroblast cultures. Elastase (from porcine pancreas) cleavage of human platelet-derived CTAP-III and rCTAP-III-Leu-21 to the des 1-15 isoforms was associated with either preservation of specific anabolic biologic activity or an actual increase in specific activity. Nonenzymatic glycosylation of lysyl residues and deamination of the NH2-terminal asparagine of platelet-derived CTAP-III were commonly present, but did not correlate with the biologic activities that were measured. Protein sequence homology shows CTAP-III and its isoforms to be members of a family of proteins (including NAP-1/II-8, MGSA, and platelet factor-4) known to be associated with growth, wound repair, inflammation, and neoplasia. The consequences of proteolytic processing reported here for CTAP-III may be characteristic of the other proteins in this group.
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PMID:Connective tissue activation. XXXIV: Effects of proteolytic processing on the biologic activities of CTAP-III. 221 61


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