Mechanotransduction in leukocyte activation: A review

Ayako Makino, Hainsworth Y. Shin, Yutaka Komai, Shunichi Fukuda, Mark Coughlin, Masako Sugihara-Seki, Geert W. Schmid-Schönbein

Research output: Contribution to journalReview articlepeer-review

46 Scopus citations


We review recent evidence which suggests that leukocytes in the circulation and in the tissue may readily respond to physiological levels of fluid shear stress in the range between about 1 and 10 dyn/cm2, a range that is below the level to achieve a significant passive, viscoelastic response. The response of activated neutrophilic leukocytes to fluid shear consists of a rapid retraction of lamellipodia with membrane detachment from integrin binding sites. In contrast, a subgroup of non-activated neutrophils may project pseudopods after exposure to fluid shear stress. The evidence suggests that G-protein coupled receptor downregulation by fluid shear with concomitant downregulation of Rac-related small GTPases and depolymerization of F-actin serves to retract the lamellipodia in conjunction with proteolytic cleavage of β2 integrin to facilitate membrane detachment. Furthermore, there exists a mechanism to up- and down-regulate the fluid shear-response, which involves nitric oxide and the second messenger cyclic guanosine monophosphate (cGMP). Many physiological activities of circulating leukocytes are under the influence of fluid shear stress, including transendothelial migration of lymphocytes. We describe a disease model with chronic hypertension that suffers from an attenuated fluid shear-response with far reaching implications for microvascular blood flow.

Original languageEnglish (US)
Pages (from-to)221-249
Number of pages29
Issue number4
StatePublished - 2007
Externally publishedYes


  • Actin
  • G-protein coupled receptor
  • Inflammation
  • Integrin
  • Lymphocytes
  • Microcirculation
  • Migration
  • Monocytes
  • Neutrophils
  • Nitric oxide
  • Normal stress
  • Pseudopod
  • Shear stress
  • cGMP

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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