Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human monocyte (M phi subset rosetting with anti RH-coated human erythrocytes via high-affinity, 72 kD receptors (FcRI+), contains the PGE2-producing immunosuppressive subpopulation, while the non-rosetting M phi subset (FcRI-) is the major plasminogen activator-producing and antigen-presenting M phi. This study gives additional evidence for the functional disparity of the FcRI- and FcRI+ M phi subsets. We are demonstrating that the normal human M phi subset isolated by rosetting via the FcRI receptor (FcRI+) produces greater quantities of tumor necrosis factor (TNF) than the non-rosetting (FcRI-) M phi. TNF production by the FcRI+ M phi subset is greater than that of the FcRI- M phi subset whether secreted (P less than .001) or cell-associated (P less than .001) TNF is assessed. The rosetting M phi subset that expresses high densities of FcRI (FcRI+) produced the majority of normal human peripheral blood M phi TNF whether the stimulation was an interferon gamma (IFN gamma) prime followed by MDP or followed by interleukin-2 (IL-2). The Fc rosetting technique itself resulted in some TNF induction in the FcRI+ M phi subset accounting for some of the increased TNF production of this subset. However, increasing the stimulation level of the FcRI very-low-density (FcRI-) M phi subset did not induce it to produce TNF levels equivalent to the moderately stimulated FcRI+ M phi subset. These data, therefore, imply that only stimulation through the type I Fc gamma receptor can augment or induce TNF activity. The difference in the M phi subset's TNF response remained even after the FcRI- M phi subset received a 2.5-fold increase in stimulation with the classical M phi induction regimen of IFN gamma plus bacterial cell wall product. Although stimulation of the FcRI+ M phi subset via crosslinking of their FcRI receptors might represent a unique TNF stimulation pathway, this stimulation does not occur in the low-density FcRI (FcRI-) M phi subset, again indicating functional disparity between these subsets. Greater TNF production by the FcRI+ M phi subset was induced concomitant to elevation of its prostaglandin E2 production. Since both TNF and PGE2 are increased in some patient groups, a pathological shift in the FcRI+ versus FcRI- M phi ratio in these patients coupled to the functional differences in FcRI+ and FcRI- M phi subsets could be one mechanism for the development of immunoincompetence.
 ...
PMID:Differential tumor necrosis factor production by human monocyte subsets. 213 48

Several functional defects have been found in neutrophils from leukocyte adhesion deficiency (LAD) patients who fail to express the CD11/CD18 leukoadhesins: Mo1, LFA-1, and p150,95. To better understand the functional defects of LAD neutrophils, we have performed capping experiments. Purified normal or LAD neutrophils were labeled with fluorochrome-conjugated concanavalin A (Con A) or F(ab')2 fragments of antiurokinase-type plasminogen activator receptor (uPAR), anti-Fc gamma RIII (CD16), anti-Mo5, and anti-CD14 antibodies. F(ab')2-labeled cells were capped using a second-step F(ab')2 fragment of an antimurine Fab antiserum. Cells were capped for 30 minutes at 37 degrees C, then observed by fluorescence microscopy. LAD neutrophils were found to be deficient in capping, but not clustering of all of the reagents tested to date. The percent of cells exhibiting capping of Con A, Fc gamma RIII, urokinase receptor, CD14, and Mo5 were 52%, 67%, 70%, 25%, and 64% for normal neutrophils but were only 10%, 5%, 2%, 3%, and 1%, respectively, for LAD neutrophils. Capping of this panel of membrane components in LAD or normal neutrophils was not augmented by the addition of either 10(-5) mol/L colchicine or 10(-7) mol/L FMLP. Because capping requires membrane-to-cytosol communication and an intact microfilament linkage, we suggest that leukoadhesins may play a broad role in promoting the redistribution of membrane components including adherence-related receptors such as Fc gamma RIII and the urokinase receptor.
 ...
PMID:Aberrant capping of membrane proteins on neutrophils from patients with leukocyte adhesion deficiency. 812 56

Because obesity leads to a state of chronic, low-grade inflammation and oxidative stress, we hypothesized that the contribution of genes to variation in a biomarker of these two processes may be influenced by the degree of adiposity. We tested this hypothesis using samples from the San Antonio Family Heart Study that were assayed for activity of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), a marker of inflammation and oxidative stress. Using an approach to model discrete genotypexenvironment (GxE) interaction, we assigned individuals to one of two discrete diagnostic states (or "adiposity environments"): nonobese or obese, according to criteria suggested by the World Health Organization. We found a genomewide maximum LOD of 3.39 at 153 cM on chromosome 1 for Lp-PLA(2). Significant GxE interaction for Lp-PLA(2) at the genomewide maximum (P=1.16 x 10(-4)) was also found. Microarray gene-expression data were analyzed within the 1-LOD interval of the linkage signal on chromosome 1. We found two transcripts--namely, for Fc gamma receptor IIA and heat-shock protein (70 kDa)--that were significantly associated with Lp-PLA(2) (P<.001 for both) and showed evidence of cis-regulation with nominal LOD scores of 2.75 and 13.82, respectively. It would seem that there is a significant genetic response to the adiposity environment in this marker of inflammation and oxidative stress. Additionally, we conclude that GxE interaction analyses can improve our ability to identify and localize quantitative-trait loci.
 ...
PMID:Genotype x adiposity interaction linkage analyses reveal a locus on chromosome 1 for lipoprotein-associated phospholipase A2, a marker of inflammation and oxidative stress. 1716 Sep 4