Secretory IgA induces antigen-independent eosinophil survival and cytokine production without inducing effector functions.
BACKGROUND
Eosinophils in human beings reside in tissues, especially the mucosal tissues of the gastrointestinal tract and inflamed airways. Secretory IgA (S-IgA) is the predominant antibody secreted by these tissues and likely plays a role in the innate immune response.


OBJECTIVE
Because eosinophils and S-IgA are often colocalized in mucosal tissues, we examined the potential regulatory effects of S-IgA without antigens on survival, gene expression, and effector functions of human eosinophils.


METHODS
Eosinophils were incubated with S-IgA in solution without antigens (soluble S-IgA) or with S-IgA immobilized to mimic multivalent antigen cross-linking. Eosinophil activation was monitored by superoxide anion generation and degranulation. Survival was assessed between 24 and 96 hours. Gene and protein expression were examined by microarray and ELISA. Eosinophil lysates were examined by immunoblot for extracellular signal-regulated kinase (ERK) phosphorylation.


RESULTS
Immobilized S-IgA stimulated eosinophil superoxide production and degranulation; soluble S-IgA did not. Although immobilized S-IgA inhibited eosinophil survival in vitro, soluble S-IgA enhanced survival; this involved autocrine production of GM-CSF. Soluble S-IgA without antigens induced increases in mRNA levels of various cytokines, chemokines, signal transduction molecules, antiapoptotic factors, and cell surface markers. By using ELISA, we confirmed protein expression of selected mediators. Eosinophil interaction with soluble S-IgA likely involves FcalphaRI (CD89) and ERK pathway activation.


CONCLUSIONS
Secretory IgA without multivalent antigens may regulate survival and gene expression of eosinophils. Eosinophils in mucosal tissues can be either primed for action (cytokine production and survival) or fully activated (degranulation and superoxide release) by different forms of S-IgA.
Bartemes
Kathleen R
KR
Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic Rochester, MN 55905, USA.
Cooper
Kate M
KM
Drain
Kerry L
KL
Kita
Hirohito
H
D015550:Cell Degranulation; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D004804:Eosinophils / Q000166:cytology* / Q000276:immunology* / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000008:administration & dosage*; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System; D012995:Solubility; D013481:Superoxides / Q000378:metabolism
D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D013481:Superoxides