Extracellular matrix proteins attenuate activation and degranulation of stimulated eosinophils

Hirohito Kita, Shiro Horie, Gerald J. Gleich

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Cellular adhesion plays an important role in the recruitment and activation of eosinophils. Here, we investigated whether extracellular matrix (ECM) proteins modify effector functions of activated human eosinophils. We coated 96-well plates with laminin or fibronectin and blocked nonspecific protein-binding sites with human serum albumin (HSA). When eosinophils were stimulated with platelet-activating factor (PAF) and incubated in these ECM- coated wells, the eosinophils adhered using both β1- and β2-integrins. Degranulation of eosinophils adherent to laminin- and fibronectin-coated wells was reduced about 50% compared with cells adherent to uncoated, HSA- blocked wells. Furthermore, these inhibitory effects of laminin and fibronectin were concentration-dependent and secretagogue-specific, that is, degranulation induced by C5a and IL-5 was inhibited while degranulation induced by secretory IgA and PMA was not inhibited. Plasma fibronectin, type I collagen and type IV collagen also inhibited PAF- and C5a-induced eosinophil degranulation, whereas fibrinogen did not. By microscopy, PAF- stimulated eosinophils, adhering to uncoated HSA-blocked wells, appeared elongated with many pseudopods. In contrast, eosinophils adhering to laminin- coated wells appeared oval with few pseudopods. Furthermore, when cells were incubated in laminin-coated wells, PAF-stimulated production of a second messenger, inositol phosphate, was markedly reduced. These findings suggest thai ECM proteins, such as laminin and fibronectin, attenuate both activation and degranulation of eosinophils and also influence their morphology after stimulation by physiologic secretagogues. Thus, ECM proteins may regulate activation of eosinophils, as they traverse between the peripheral blood and their targets.

Original languageEnglish (US)
Pages (from-to)1174-1181
Number of pages8
JournalJournal of Immunology
Volume156
Issue number3
StatePublished - Feb 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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