Effects of leukocyte activation on capillary hemodynamics in skeletal muscle

Harris, A. G.; Skalak, Thomas C.

doi:10.1152/ajpheart.1993.264.3.h909

Cited by 36 publications

(41 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, the increase in resistance with WBC stiffening will diminish as diameters become larger. Increased capillary plugging and resistance to flow in the spinotrapezius muscle has been shown in response to superfusion with fMLP, where a 20% increase in capillary resistance was attributed to fMLP activation (22,23), which is similar to that found here.…”

supporting

confidence: 87%

Shedding of the endothelial glycocalyx in arterioles, capillaries, and venules and its effect on capillary hemodynamics during inflammation

Lipowsky

Gao

Lescanic

2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Lipowsky HH, Gao L, Lescanic A. Shedding of the endothelial glycocalyx in arterioles, capillaries, and venules and its effect on capillary hemodynamics during inflammation. Am J Physiol Heart Circ Physiol 301: H2235-H2245, 2011. First published September 16, 2011 doi:10.1152/ajpheart.00803.2011The endothelial glycocalyx has been identified as a barrier to transvascular exchange of fluid, macromolecules, and leukocyte-endothelium [endothelial cell (EC)] adhesion during the inflammatory process. Shedding of glycans and structural changes of the glycocalyx have been shown to occur in response to several agonists. To elucidate the effects of glycan shedding on microvascular hemodynamics and capillary resistance to flow, glycan shedding in microvessels in mesentery (rat) was induced by superfusion with 10 Ϫ7 M fMLP. Shedding was quantified by reductions of fluorescently labeled lectin (BS-1) bound to the EC and reductions in thickness of the barrier to infiltration of 70-kDa dextran on the EC surface. Red cell velocities (two-slit technique), pressure drops (dual servo-null method), and capillary hematocrit (direct cell counting) were measured in parallel experiments. The results indicate that fMLP caused shedding of glycans in all microvessels with reductions in thickness of the barrier to 70-kDa dextran of 110, 80, and 123 nm, in arterioles, capillaries, and venules, respectively.

show abstract

supporting

confidence: 87%

Shedding of the endothelial glycocalyx in arterioles, capillaries, and venules and its effect on capillary hemodynamics during inflammation

Lipowsky

Gao

Lescanic

2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…LFA1 may remain intact, even under FSS, to enable neutrophils to interact loosely with the microvascular wall as part of their immune-surveillance function. In contrast, Mac1-related binding may represent a key checkpoint against commitment into the acute inflammatory cascade that is subject to FSS control to prevent neutrophils from adhering to vessels under nonpathogenic conditions, a situation that may adversely alter tissue perfusion by either a rheological effect on peripheral resistance [33,34] or a pathobiological action on endothelial vasomotor control [35].…”

Section: Discussionmentioning

confidence: 99%

Fluid shear-induced cathepsin B release in the control of Mac1-dependent neutrophil adhesion

Akenhead

Fukuda

Schmid‐Schönbein

et al. 2017

Journal of Leukocyte Biology

View full text Add to dashboard Cite

There is compelling evidence that circulatory hemodynamics prevent neutrophil activation, including adhesion to microvessels, in the microcirculation. However, the underlying mechanism or mechanisms by which that mechanoregulation occurs remain unresolved. Here, we report evidence that exposure to fluid shear stress (FSS) promotes neutrophils to release cathepsin B (ctsB) and that this autocrine regulatory event is antiadhesive for neutrophils on endothelial surfaces through Mac1-selective regulation. We used a combined cellengineering and immunocytochemistry approach to find that ctsB was capable of cleaving Mac1 integrins on neutrophils and demonstrated that this proteolysis alters their adhesive functions. Under no-flow conditions, ctsB enhanced neutrophil migration though a putative effect on pseudopod retraction rates. We also established a flow-based cell detachment assay to verify the role of ctsB in the control of neutrophil adhesion by fluid flow stimulation. Fluid flow promoted neutrophil detachment from platelet and endothelial layers that required ctsB, consistent with its fluid shear stress-induced release. Notably, compared with leukocytes from wild-type mice, those from ctsBdeficient (ctsB 2/2 ) mice exhibited an impaired CD18 cleavage response to FSS, significantly elevated baseline levels of CD18 surface expression, and an enhanced adhesive capacity to mildly inflamed postcapillary venules. Taken together, the results of the present study support a role for ctsB in a hemodynamic control mechanism that is antiadhesive for leukocytes on endothelium. These results have implications in the pathogenesis of chronic inflammation, microvascular dysfunction, and cardiovascular diseases involving sustained neutrophil activation in the blood and microcirculation.

show abstract

“…Activated circulating leukocytes cause significant flow reduction in capillaries (2) to the point of complete stasis and microvascular entrapment (4,29). In contrast, the projection of pseudopods becomes enhanced after cessation of blood flow and a reduction of shear stress on leukocytes.…”

Section: Figmentioning

confidence: 99%

The leukocyte response to fluid stress

Moazzam

DeLano

Zweifach

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

182

201

View full text Add to dashboard Cite

Leukocyte migration from a hemopoietic pool across marrow endothelium requires active pseudopod formation and adhesion. Leukocytes rarely show pseudopod formation while in circulation. At question then is the mechanism that serves to minimize leukocyte pseudopod formation in the circulation. We tested the hypothesis that fluid shear stress acts to prevent pseudopod formation. When individual human leukocytes (neutrophils, monocytes) spreading on glass surfaces in vitro were subjected to fluid shear stress (Ϸ1 dyn͞cm 2 ), an instantaneous retraction of pseudopods was observed. Removal of the fluid shear stress in turn led to the return of pseudopod projection and cell spreading. When steady shear stress was prolonged over several minutes, leukocyte swelling occurs together with an enhanced random motion of cytoplasmic granules and a reduction of cytoplasmic stiffness. The response to shear stress could be suppressed by K ؉ channel blockers and chelation of external Ca 2؉ . In rat mesentery microvessels after occlusion, circulating leukocytes project pseudopods in free suspension or when attached to the endothelium, even though immediately after occlusion only few pseudopods were present. When flow was restored, pseudopods on adhering leukocytes were retracted and then the cells began to roll and detach from the endothelium. In conclusion, plasma shear stress in the circulation serves to reduce pseudopod projection and adhesion of circulating leukocytes and vice versa reduction of shear stress leads to pseudopod projection and spreading of leukocytes on the endothelium.Under physiological conditions, most circulating leukocytes in the blood stream exhibit low levels of pseudopod projection or expression of membrane molecules for adhesion to endothelium. Projection of pseudopods is associated with F-actin formation and cytoplasm stiffening (1). Leukocytes with pseudopods show enhanced resistance to flow in microvessels (2) to the point of complete capillary arrest (3, 4). In contrast, leukocytes require activation and projection of pseudopods (also referred to as lamellipods or microvilli) to migrate from their hemopoietic compartment of origin across marrow endothelium into the circulation (5). Migration across the peripheral vascular endothelium also requires active pseudopod formation and adhesion. Rheological studies of leukocytes under static conditions have yielded higher values for the cytoplasmic properties than under in vivo conditions, when they are subject to physiological shear stress prior to deformation (6). The evidence thus suggests that in the circulation a mechanism exists for shifting leukocytes from active pseudopod projection to a more passive state without pseudopods.Endothelial cells (7,8), erythrocytes (9), and platelets (10) are shear sensitive. Shear stress and shear stress gradients (11) serve to modulate endothelial cell shape as well as orientation of the cytoskeletal actin and tubulin network, membrane ion transport, endocytosis, and gene expression (12-15) and ␤ 2 integrin-med...

show abstract

Effects of leukocyte activation on capillary hemodynamics in skeletal muscle

Cited by 36 publications

References 0 publications

Shedding of the endothelial glycocalyx in arterioles, capillaries, and venules and its effect on capillary hemodynamics during inflammation

Shedding of the endothelial glycocalyx in arterioles, capillaries, and venules and its effect on capillary hemodynamics during inflammation

Fluid shear-induced cathepsin B release in the control of Mac1-dependent neutrophil adhesion

The leukocyte response to fluid stress

Contact Info

Product

Resources

About