A role for endothelial selectins in allergic and nonallergic inflammatory disease.
BACKGROUND
Several studies indicate that selectin-mediated leukocyte migration may depend on the types of initiating inflammatory stimuli or on the vascular beds involved in the inflammatory response. Thus, targeting selectin interactions to treat inflammation may have variable effects depending on the site and origin of the inflammatory response.


OBJECTIVE
To address whether selectin-mediated leukocyte recruitment is stimulus or tissue dependent.


METHODS
We examined pulmonary and cutaneous allergic inflammatory responses and silica-induced nonallergic lung inflammation and fibrosis in wild-type and P- and E-selectin-deficient (P/E-/-) double knockout mice. Allergen-sensitized wild-type and P/E-/- double knockout mice were challenged either intradermally or via the airways to induce allergic responses in the skin or lung, respectively. Other animals were subjected to intranasal silica administration to induce a nonallergic lung inflammatory/fibrotic response.


RESULTS
The P/E-/- mice exhibited significantly reduced allergic inflammation in the skin and lung. Allergic late-phase ear swelling and allergic lung airway hyperresponsiveness were also significantly attenuated in the P/E-/- mice compared with identically treated wild-type animals. In contrast, pulmonary inflammation and fibrosis induced by intranasal administration of silica particles resulted in a more severe phenotype in the P/E-/- mice.


CONCLUSIONS
Selectin interactions drive allergic inflammation in the lung and skin. Silica-induced pulmonary inflammation and fibrosis, however, was more pronounced in the absence of selectin interactions, suggesting that selectin-mediated leukocyte migration may depend on the types of initiating inflammatory stimuli.
Jiao
Aiping
A
Department of Respiratory Diseases, Wyeth Research, Cambridge, Massachusetts 02140, USA.
Fish
Susan C
SC
Mason
Lawrence E
LE
Schelling
Scott H
SH
Goldman
Samuel J
SJ
Williams
Cara M M
CM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism*; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D019007:P-Selectin / Q000276:immunology* / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity; D012867:Skin / Q000276:immunology
D016207:Cytokines; D019040:E-Selectin; D019007:P-Selectin; D012822:Silicon Dioxide; D010047:Ovalbumin