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Blood, Vol. 93 No. 2 (January 15), 1999:
pp. 580-589
Selective Requirements for Leukocyte Adhesion Molecules in Models of
Acute and Chronic Cutaneous Inflammation: Participation of E- and P-
But Not L-Selectin
Michelle D. Catalina,
Pila Estess, and
Mark H. Siegelman
From the Laboratory of Molecular Pathology, Department of Pathology,
The University of Texas Southwestern Medical Center at Dallas, Dallas,
TX.
Adhesion molecules borne by both endothelial cells and circulating
leukocytes are in large measure responsible for guiding the process of
extravasation. The selectin family has been primarily associated with
the early stages of adhesion involving initial contact and rolling. A
significant body of evidence has accumulated indicating a fundamental
role for the endothelial members of this family, E- and P-selectin, in
a variety of inflammatory states and models. Although originally
identified as the lymph node-specific lymphocyte homing receptor,
L-selectin has also been suggested to play an important role in
leukocyte recruitment to sites of inflammation. We have recently
demonstrated, using L-selectin-deficient mice, that defects in contact
hypersensitivity (CHS) responses are in essence due to the inability of
T cells to home to and be sensitized within peripheral lymph nodes,
whereas nonspecific effector cells are fully capable of entry into
sites of cutaneous inflammation (Catalina et al, J Exp Med
184:2341, 1996). In the present study, we perform an
analysis of adhesion molecule usage in two models of skin inflammation
and show in both L-selectin-deficient as well as wild-type mice that a
combination of P- and E-selectin is crucial for the development of both
acute (croton oil) and chronic (contact hypersensitivity) inflammation
at sites of the skin, whereas L-selectin does not appear to play a
significant role. Moreover,  4 integrins are shown to be
integral to a CHS but not an acute irritant response, whereas CD44 does
not significantly contribute to either. These results provide a
systematic examination in one study of major adhesion molecules that
are critical in acute and chronic skin inflammation. They reinforce the
essential role of the collaboration of E- and P-selectin in both
specific and nonspecific skin inflammatory responses and the importance of 4 in the specific response only. In addition, they substantiate only a limited role, if any, for L-selectin in these cutaneous effector
mechanisms and demonstrate the essential equivalence in this analysis
of L-selectin-deficient mice compared with normal mice treated with
blocking antibodies.
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