TY - JOUR T1 - Neutrophil Inhibitory Factor Abrogates Neutrophil Adhesion by Blockade of CD11a and CD11b β<sub>2</sub> Integrins JF - Molecular Pharmacology JO - Mol Pharmacol SP - 926 LP - 932 DO - 10.1124/mol.56.5.926 VL - 56 IS - 5 AU - Siu K. Lo AU - Arshad Rahman AU - Ning Xu AU - Ming Yuan Zhou AU - Pablito Nagpala AU - Howard A. Jaffe AU - Asrar B. Malik Y1 - 1999/11/01 UR - http://molpharm.aspetjournals.org/content/56/5/926.abstract N2 - We studied the basis of inhibition of polymorphonuclear leukocyte (PMN) adhesion induced by neutrophil inhibitory factor (NIF), a 41-kDa CD11/CD18 β2 integrin-binding protein isolated from the canine hookworm (Ancylostoma caninum). NIF blocked PMN adhesion in a concentration-dependent manner with complete blockade occurring at ∼10 nM NIF. Because CD11a and CD11b β2integrins are functionally active on stimulated PMNs, and yet NIF is postulated to inhibit only CD11b integrin by binding to its I domain, we evaluated the contributions of CD11a and CD11b β2integrins in the mechanism of inhibition of PMN adhesion to endothelial cells. We observed an additive inhibitory effect (&gt;90% inhibition) of PMN adhesion to endothelial cells when NIF was used in combination with anti-CD11b monoclonal antibodies, which alone at saturating concentrations reduced PMN adhesion by only 50%. NIF also prevented aggregation of phorbol ester-stimulated JY lymphoblastoid cells that expressed only the functionally active CD11a, suggesting that NIF also can inhibit CD11a-dependent response. We transduced the NIF cDNA into human dermal microvessel endothelial cells in which NIF synthesis and release prevented PMN adhesion to the transduced human dermal microvessel endothelial cells. These data indicated that the potent antiadhesive effect of NIF may be the result of inhibition of CD11a and CD11b β2 integrins on PMNs. Moreover, the strategy of NIF release from transduced endothelial cells suggests the feasibility of blocking the CD11a- and CD11b β2integrin-dependent PMN adhesion and PMN migration responses specifically at sites of endothelial cell activation. ER -