Blood cell dynamics in P-selectin-deficient mice

R. C. Johnson, T. N. Mayadas, Paul S. Frenette, R. E. Mebius, M. Subramaniam, A. Lacasce, R. O. Hynes, D. D. Wagner

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

P-selectin is expressed on the surfaces of activated platelets and endothelium where it mediates binding to leukocytes. P-selectin-deficient mice were shown to exhibit peripheral neutrophilia (Mayadas et al: Cell 74:541, 1993). We now show that this is not caused by changes in bone marrow precursors nor by a lack of neutrophil margination. Both P-selectin-positive and -negative animals displayed similar increases in peripheral blood neutrophil numbers after injection of epinephrine. However, clearance of 51Chromium-labeled neutrophils is delayed in mice deficient for P-selectin, indicating that the neutrophilia is at least in part the result of delayed removal. We detected no obvious alterations in lymphocyte differentiation, distribution, or adhesion to high endothelial venules in peripheral lymph nodes. Through intravital microscopy, we examined the impact of P-selectin deficiency on leukocyte/endothelial interaction beyond the initial stages of inflammation. Four hours after the administration of an inflammatory irritant, leukocyte rolling was observed even in the absence of P-selectin. There were significantly fewer rolling cells relative to wild-type mice, and their velocity was reduced. Moreover, in the peritonitis model, the number of peritoneal macrophages in wild-type mice increased threefold at 48 hours, whereas the macrophages in the mutant mice remained near baseline levels. Thus, whereas P-selectin is known to be involved in early stages of an inflammatory response, our results indicate that it is additionally responsible for leukocyte rolling and macrophage recruitment in more prolonged tissue injury.

Original languageEnglish (US)
Pages (from-to)1106-1114
Number of pages9
JournalBlood
Volume86
Issue number3
StatePublished - 1995
Externally publishedYes

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P-Selectin
Blood Cells
Blood
Cells
Macrophages
Leukocyte Rolling
Neutrophils
Leukocytes
Venules
Lymphocytes
Irritants
Peritoneal Macrophages
Platelets
Peritonitis
Epinephrine
Endothelium
Bone
Animals
Blood Platelets
Adhesion

ASJC Scopus subject areas

  • Hematology

Cite this

Johnson, R. C., Mayadas, T. N., Frenette, P. S., Mebius, R. E., Subramaniam, M., Lacasce, A., ... Wagner, D. D. (1995). Blood cell dynamics in P-selectin-deficient mice. Blood, 86(3), 1106-1114.

Blood cell dynamics in P-selectin-deficient mice. / Johnson, R. C.; Mayadas, T. N.; Frenette, Paul S.; Mebius, R. E.; Subramaniam, M.; Lacasce, A.; Hynes, R. O.; Wagner, D. D.

In: Blood, Vol. 86, No. 3, 1995, p. 1106-1114.

Research output: Contribution to journalArticle

Johnson, RC, Mayadas, TN, Frenette, PS, Mebius, RE, Subramaniam, M, Lacasce, A, Hynes, RO & Wagner, DD 1995, 'Blood cell dynamics in P-selectin-deficient mice', Blood, vol. 86, no. 3, pp. 1106-1114.
Johnson RC, Mayadas TN, Frenette PS, Mebius RE, Subramaniam M, Lacasce A et al. Blood cell dynamics in P-selectin-deficient mice. Blood. 1995;86(3):1106-1114.
Johnson, R. C. ; Mayadas, T. N. ; Frenette, Paul S. ; Mebius, R. E. ; Subramaniam, M. ; Lacasce, A. ; Hynes, R. O. ; Wagner, D. D. / Blood cell dynamics in P-selectin-deficient mice. In: Blood. 1995 ; Vol. 86, No. 3. pp. 1106-1114.
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