Physical interactions between mast cells and eosinophils: a novel mechanism enhancing eosinophil survival in vitro.
BACKGROUND
Mast cells (MCs) and eosinophils (Eos) are the key effector cells of the allergic reaction. Although classically associated with different stages of the response, the cells co-exist in the inflamed tissue in the late and chronic phases in high numbers and are likely to cross-talk. While some mediators of MCs are known to affect Eos biology and vice versa, paracrine and physical interplay between the two cells has not been described yet. We aimed to investigate whether intercellular MC-Eos communication could take place in the allergic response and exert functional bidirectional changes on the cells.


METHODS
Tissue sections from various allergic disorders were specifically stained for both cells. Human cord blood-derived MCs and peripheral blood Eos, co-cultured under different conditions, were studied by advanced microscopy and flow cytometry.


RESULTS
Several co-localized MC-Eos pairs were detected in human nasal polyps and asthmatic bronchi, as well in mouse atopic dermatitis. In vitro, MCs and Eos formed stable conjugates at high rates, with clear membrane contact. In the presence of MCs, Eos were significantly more viable under several co-culture conditions and at both IgE-activated and steroid-inhibited settings. MC regulation of Eos survival required communication through soluble mediators but was even more dependent on physical cell-cell contact.


CONCLUSIONS
Our findings provide the first evidence for a complex network of paracrine and membrane interactions between MCs and Eos. The prosurvival phenotype induced by this MC-Eos interplay may be critical for sustaining chronic allergic inflammation.
Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
M
M
Elishmereni
H T
HT
Alenius
P
P
Bradding
S
S
Mizrahi
A
A
Shikotra
Y
Y
Minai-Fleminger
D
D
Mankuta
R
R
Eliashar
G
G
Zabucchi
F
F
Levi-Schaffer
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000071178:CD48 Antigen; D002450:Cell Communication / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D019899:Paracrine Communication / Q000187:drug effects; D011971:Receptors, Immunologic / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family
D015703:Antigens, CD; D000071178:CD48 Antigen; C490007:Cd244a protein, mouse; D016207:Cytokines; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D007073:Immunoglobulin E; D003907:Dexamethasone