title: Matrix metalloproteinases modulate ameboid-like migration of neutrophils through inflamed interstitial tissue.
abstract: In vitro studies suggest that leukocytes locomote in an ameboid fashion independently of pericellular proteolysis. Whether this motility pattern applies for leukocyte migration in inflamed tissue is still unknown. In vivo microscopy on the inflamed mouse cremaster muscle revealed that blockade of serine proteases or of matrix metalloproteinases (MMPs) significantly reduces intravascular accumulation and transmigration of neutrophils. Using a novel in vivo chemotaxis assay, perivenular microinjection of inflammatory mediators induced directional interstitial migration of neutrophils. Blockade of actin polymerization, but not of actomyosin contraction abolished neutrophil interstitial locomotion. Multiphoton laser scanning in vivo microscopy showed that the density of the interstitial collagen network increases in inflamed tissue, thereby providing physical guidance to infiltrating neutrophils. Although neutrophils locomote through the interstitium without pericellular collagen degradation, inhibition of MMPs, but not of serine proteases, diminished their polarization and interstitial locomotion. In this context, blockade of MMPs was found to modulate expression of adhesion/signaling molecules on neutrophils. Collectively, our data indicate that serine proteases are critical for neutrophil extravasation, whereas these enzymes are dispensable for neutrophil extravascular locomotion. By contrast, neutrophil interstitial migration strictly relies on actin polymerization and does not require the pericellular degradation of collagen fibers but is modulated by MMPs.
authors.affiliation: Walter Brendel Centre for Experimental Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Lerchenberger
authors.forename: Bernd
authors.initials: B
authors.lastname: Uhl
authors.forename: Konstantin
authors.initials: K
authors.lastname: Stark
authors.forename: Gabriele
authors.initials: G
authors.lastname: Zuchtriegel
authors.forename: Annekathrin
authors.initials: A
authors.lastname: Eckart
authors.forename: Meike
authors.initials: M
authors.lastname: Miller
authors.forename: Daniel
authors.initials: D
authors.lastname: Puhr-Westerheide
authors.forename: Marc
authors.initials: M
authors.lastname: Praetner
authors.forename: Markus
authors.initials: M
authors.lastname: Rehberg
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Khandoga
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
authors.forename: Fritz
authors.initials: F
authors.lastname: Krombach
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Reichel
mesh_terms: D000614:Aminocaproates / Q000494:pharmacology; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D007154:Immune System Diseases / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D007960:Leukocyte Disorders / Q000378:metabolism / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D010538:Peritonitis / Q000276:immunology / Q000473:pathology; D014148:Tranexamic Acid / Q000494:pharmacology; D057688:Transcellular Cell Migration / Q000187:drug effects / Q000276:immunology
chemical_list: D000614:Aminocaproates; D014148:Tranexamic Acid; D007611:Aprotinin; D020782:Matrix Metalloproteinases