Anti-Cd45 Antibody Enhances Lipoxygenase Pathway of Human Naive Mononuclear Cells and Cyclooxygenase Pathway of Neutrophils

Objective and Design: Anti-CD45 antibody exhibits multiple biological effects on human mononuclear cells (MNC) and polymorphonuclear neutrophils (PMN). We intended to determine whether anti-CD45 antibody could affect arachidonic acid metabolism and thereby, the interactions between human naive MNC and PMN. Materials and Methods: Human naive MNC and PMN were incubated with monoclonal anti- human CD45 IgG F(ab')(2) antibody or non- specific IgG F(ab' )(2) for 30 min. The mRNA expression of cyclooxygenase type 1(COX-1), type 2 (COX-2), 5-lipoxygenase (5-LOX) and leukotriene A, hydrolase (LTA(4) hydrolase) in both cells was detected by RT-PCR and quantified by densitometric determination. The presence of COX-1 and COX-2 molecules in the cells was detected by Western blot. The concentration of PGE(2) and LTB4 in cultured supernatants was measured by EIA kits. Results: Anti-CD45 IgG F(ab')2 up-regulated LTA(4) hydrolase mRNA expression and LTB4 production, but down- regulated COX-1 and COX-2 mRNA expression and PGE2 production, of naive MNC compared to non-specific IgG F(ab') (2). In contrast, a reverse modulation by the specific antibody on PMN was observed including up-regulation of cyclooxygenase pathway and down-regulation of lipoxygenase pathway. Conclusions: A novel activity of anti-CD45 with reverse modulation on cyclooxygenase/lipoxygenase pathways was found such that the expression of COX-1 and COX-2 in PMN , and 5-LOX and LTA(4) hydrolase in MNC were enhanced