Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro.

TLDR

Neutrophil adhesion to endothelial cells relies on CD11/CD18 integrins interacting with ICAM‑1 on the endothelium. The study used subunit‑specific monoclonal antibodies against CD18 heterodimers to probe this interaction in vitro. Unstimulated neutrophils attach to ICAM‑1 via LFA‑1 (blocked by anti‑CD11a), while fMLP‑stimulated cells use both LFA‑1 and Mac‑1 (blocked by anti‑CD11b), and combined blockade reduces adhesion to control protein levels.

Abstract

The adherence of human neutrophils to human umbilical vein endothelial cells (HUVEC) is partially dependent on the CD11/CD18 family of glycoproteins on the neutrophil and ICAM-1 on the HUVEC. The CD18 heterodimer involved in this adherence was evaluated in vitro using subunit-specific monoclonal antibodies (MAbs). The adherence of unstimulated neutrophils to IL-1-stimulated HUVEC was significantly inhibited by anti-CD11a but not CD11b MAbs, while the adherence of fMLP-stimulated neutrophils was significantly inhibited by both anti-CD11a and -CD11b. Anti-CD11a, but not anti-CD11b MAbs, reduced the adherence of unstimulated neutrophils on purified ICAM-1 to the same low level untreated neutrophils exhibited on a control protein, glycophorin. Stimulation with fMLP significantly increased neutrophil attachment to purified ICAM-1, but not to the control protein. Anti-CD11b MAbs reduced this chemotactically augmented adherence to that of unstimulated neutrophils, and in combination with anti-CD11a MAbs reduced adherence to that on the control protein. The results in this report indicate that unstimulated neutrophils exhibit LFA-1-dependent attachment to ICAM-1, and chemotactic stimulation enhances the attachment of human neutrophils to ICAM-1 by a Mac-1-dependent process.