Mechanisms and regulation of polymorphonuclear leukocyte and eosinophil adherence to human airway epithelial cells

Polymorphonuclear leukocytes;(PMN) and eosinophils (Eos) are important cell ular participants in a variety of acute and chronic inflammatory reactions in the airway. Histologic evidence has implicated direct interactions betwe en these two subsets of leukocytes and airway epithelial cells during infla mmation. A comprehensive characterization and comparison of physiologic sti muli and adhesion molecule involvement in granulocyte-epithelial-cell inter actions done with nontransformed human airway epithelial cells has not been reported. We therefore examined the regulation and biochemical mechanisms governing granulocyte-epithelial-cell adhesion, using either purified PMN o r Eos and primary cultures of human bronchial epithelial cells (HBECs). We investigated the involvement of a number of proinflammatory signals associa ted with allergic and nonallergic airway inflammation, as well as the contr ibution of several epithelial and leukocyte adhesion molecules, including i ntercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule- 1 (VCAM-1), and members of the beta(1), beta(2), and beta(7) integrin famil ies. ICAM-1 was expressed at low levels on cultured HBECs and was markedly upregulated after stimulation with interferon (IFN)-gamma or, to a lesser e xtent, with tumor necrosis factor (TNF)-alpha or interleukin (IL)-1. VCAM-1 was not present on resting HBECs, and was not upregulated after stimulatio n with IFN-gamma,IL-1, IL-4, or TNF-alpha. PMN adhesion to HBECs could be i nduced either through activation of PMN with IL-X, granulocyte-macrophage c olony-stimulating factor (GM-CSF),or C5a, but not with IL-5 or by preactiva tion of HBECs with TNF-alpha or IFN-gamma. Blocking antibody studies indica ted that PMN-HBEC adherence depended on beta(2), integrins, primarily or al pha(M)beta(2) (Mac-I). Adherence of Eos to HBECs could be induced through a ctivation of Eos with IL-5, GM-CSF, or C5a, but not with IL-8 or by prior a ctivation of HBECs with TNF-alpha of IFN-gamma. Maximal adhesion of Eos and PMN required pretreatment of HBECs with either TNF-alpha or IFN-gamma in a ddition to leukocyte activation. Adherence of Eos to unstimulated HBECs was mediated through both beta(1) and beta(2) integrins, whereas adhesion of E os to activated HBECs was dominated by beta(2) integrins. Adhesion of both Eos and PMN was inhibited by treatment of HBECs with blocking antibodies to ICAM-1. Differential utilization of beta(1) and beta(2) integrins by Eos, depending on the activation state of the epithelium, is a novel finding and may affect activation and/or recruitment of Eos in airway tissue. Mechanis ms of adhesion of HBECs to Eos and PMN, as evidenced by the different respo nsiveness of the two latter types of cells to IL-8 and IL-5, may account fo r a prevalence of Eos over PMN in certain airway diseases.