H2-Calponin Regulates Adhesion and Migration of Macrophages

Abstract

Calponin is an actin filament-associated regulatory protein. The h2 isoform of calponin is found in both smooth muscle and non-muscle cells including monocytes and macrophages. We previously demonstrated that h2-calponin plays an inhibitory role in the regulation of cell proliferation and migration and increases the stability of actin cytoskeleton (Hossain et al., AJP: 284:C156-67, 2003; JBC 280:42442-53, 2005; Biochemistry 45:15670-83, 2006). Using residential cells isolated from the intraperitoneal cavity of h2-calponin knockout mice (Huang et al., JBC 283:25887-99, 2008), the present study investigated the role of h2-calponin in macrophage motility. Substrate adhesion of h2-calponin-null macrophages was significantly decreased together with reduced cell spreading area in culture dish. The h2-calponin deficient macrophages further exhibited increased migration and transendothelial migration. The deficiency of h2-calponin did not affect macrophage invasion into Matrigel, suggesting that the increased transendothelial migration is based on unchanged activity of extracellular proteases. H2-calponin was co-localized with F-actin in thin spikes at all edges of stationary macrophages and the trailing edges of migrating cells while absent in the leading edge lamellipodium. Consistent with increased motility, h2-calponin-null macrophages exhibited losses of these anchoring spikes. The results suggest a role of h2-calponin in inhibiting macrophage motility and transendothelial migration through stabilization of actin cytoskeleton.