title: Leukocyte cytoskeletal structure determines capillary plugging and network resistance.
abstract: Leukocyte plugging in capillaries may play an important role in microvascular hemodynamics under pathological conditions that result in leukocyte activation. Previous studies have quantified the effects of transient capillary plugging on microvascular resistance for control and activated leukocytes, but have not focused on the intracellular mechanisms responsible. The frequency and duration of leukocyte-capillary plugging were measured throughout capillary networks in spinotrapezius muscle of anesthetized rats under normal physiological conditions and after leukocyte activation coupled with cytoskeletal F-actin depolymerization, using superfusion with 10(-7) M N-formyl-methionyl-leucyl-phenylalanine (FMLP) and 0.3 microM cytochalasin D (CD). These data were used to estimate the increase in microvascular flow resistance due to leukocyte plugging. The increase was 1.1% in control and 0.7% in the activated FMLP-CD state and was not significantly different. CD abolished the previously reported 16% resistance increase caused by FMLP activation [Harris and Skalak, Am. J. Physiol. 264 (Heart Circ. Physiol. 31): H909-H916, 1993.], suggesting that leukocyte plugging in capillaries is primarily determined by leukocyte cytoplasmic viscosity and is not significantly affected by cell adhesion. Thus F-actin-mediated cytoskeletal reorganization during leukocyte activation has significant impact on microvascular resistance.
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville 22908.
authors.forename: A G
authors.initials: AG
authors.lastname: Harris
authors.forename: T C
authors.initials: TC
authors.lastname: Skalak
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002196:Capillaries / Q000502:physiology*; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D005260:Female; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009132:Muscles / Q000098:blood supply*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance
chemical_list: D000199:Actins; D015638:Cytochalasin D; D009240:N-Formylmethionine Leucyl-Phenylalanine