Osteopontin is expressed and functional in human eosinophils.
BACKGROUND
Eosinophils are critically involved in allergic inflammation and tissue remodeling. Osteopontin (OPN) is a glycoprotein molecule which exhibits pro-fibrogenic and pro-angiogenic properties and has recently also been implicated in allergic diseases. In this study, we investigated the expression and function of OPN in human eosinophils.


METHODS
Osteopontin mRNA (RT-PCR) and protein (immunofluorescence) expression in peripheral blood eosinophils from atopic human subjects were evaluated. Soluble OPN release was determined in resting and activated eosinophils. The contribution of OPN to eosinophil-induced angiogenesis was determined using the chick embryo chorio- allantoic membrane (CAM) assay and OPN-induced eosinophil chemotaxis was determined (ChemoTx System microplate wells). Finally, OPN expression in bronchoalveolar lavage (BAL) fluids from mild asthmatic and normal control subjects was determined.


RESULTS
Osteopontin is expressed in human eosinophils and is increased following GM-CSF and IL-5 activation. Eosinophil-derived OPN contributes to eosinophil-induced angiogenesis. Recombinant OPN promotes eosinophil chemotaxis in vitro and this effect is mediated by alpha(4)beta(1) integrin binding. Soluble OPN is increased in the bronchoalveolar lavage fluid from mild asthmatic subjects and correlates with eosinophil counts.


CONCLUSIONS
We therefore conclude that OPN is likely to contribute to the process of angiogenesis observed in the airways in asthma.
Puxeddu
I
I
Department of Pharmacology and Experimental Therapeutics, The Hebrew University of Jerusalem, Israel.
Berkman
N
N
Ribatti
D
D
Bader
R
R
Haitchi
H M
HM
Davies
D E
DE
Howarth
P H
PH
Levi-Schaffer
F
F
D000293:Adolescent; D000328:Adult; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D002642:Chick Embryo; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology; D053495:Osteopontin / Q000096:biosynthesis* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D012333:RNA, Messenger; D053495:Osteopontin