Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. May 1, 1996; 183(5): 2329–2336.
PMCID: PMC2192541

Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice

Abstract

During the initial phase of the inflammatory response, leukocytes marginate and roll along the endothelial surface, a process mediated largely by the selectins and their ligands. Mice with mutations in individual selectins show no spontaneous disease and have mild or negligible deficiencies of inflammatory responses. In contrast, we find that mice with null mutations in both endothelial selectins (P and E) develop a phenotype of leukocyte adhesion deficiency characterized by mucocutaneous infections, plasma cell proliferation, hypergammaglobulinemia, severe deficiencies of leukocyte rolling in cremaster venules with or without addition of TNF-alpha, and an absence of neutrophil emigration at 4 h in response to intraperitoneal Streptococcus pneumoniae peritonitis. These mice provide strong evidence for the functional importance of selectins in vivo.

Full Text

The Full Text of this article is available as a PDF (3.8M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994 Jan 28;76(2):301–314. [PubMed]
  • Albelda SM, Smith CW, Ward PA. Adhesion molecules and inflammatory injury. FASEB J. 1994 May;8(8):504–512. [PubMed]
  • Bevilacqua MP, Nelson RM. Selectins. J Clin Invest. 1993 Feb;91(2):379–387. [PMC free article] [PubMed]
  • Steegmaier M, Levinovitz A, Isenmann S, Borges E, Lenter M, Kocher HP, Kleuser B, Vestweber D. The E-selectin-ligand ESL-1 is a variant of a receptor for fibroblast growth factor. Nature. 1995 Feb 16;373(6515):615–620. [PubMed]
  • Sako D, Chang XJ, Barone KM, Vachino G, White HM, Shaw G, Veldman GM, Bean KM, Ahern TJ, Furie B, et al. Expression cloning of a functional glycoprotein ligand for P-selectin. Cell. 1993 Dec 17;75(6):1179–1186. [PubMed]
  • Brustein M, Kraal G, Mebius RE, Watson SR. Identification of a soluble form of a ligand for the lymphocyte homing receptor. J Exp Med. 1992 Nov 1;176(5):1415–1419. [PMC free article] [PubMed]
  • Lasky LA, Singer MS, Dowbenko D, Imai Y, Henzel WJ, Grimley C, Fennie C, Gillett N, Watson SR, Rosen SD. An endothelial ligand for L-selectin is a novel mucin-like molecule. Cell. 1992 Jun 12;69(6):927–938. [PubMed]
  • Van der Vieren M, Le Trong H, Wood CL, Moore PF, St John T, Staunton DE, Gallatin WM. A novel leukointegrin, alpha d beta 2, binds preferentially to ICAM-3. Immunity. 1995 Dec;3(6):683–690. [PubMed]
  • Etzioni A. Adhesion molecule deficiencies and their clinical significance. Cell Adhes Commun. 1994 Jul;2(3):257–260. [PubMed]
  • Anderson DC, Springer TA. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med. 1987;38:175–194. [PubMed]
  • Anderson DC, Schmalsteig FC, Finegold MJ, Hughes BJ, Rothlein R, Miller LJ, Kohl S, Tosi MF, Jacobs RL, Waldrop TC, et al. The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features. J Infect Dis. 1985 Oct;152(4):668–689. [PubMed]
  • Etzioni A, Frydman M, Pollack S, Avidor I, Phillips ML, Paulson JC, Gershoni-Baruch R. Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency. N Engl J Med. 1992 Dec 17;327(25):1789–1792. [PubMed]
  • Frydman M, Etzioni A, Eidlitz-Markus T, Avidor I, Varsano I, Shechter Y, Orlin JB, Gershoni-Baruch R. Rambam-Hasharon syndrome of psychomotor retardation, short stature, defective neutrophil motility, and Bombay phenotype. Am J Med Genet. 1992 Oct 1;44(3):297–302. [PubMed]
  • Price TH, Ochs HD, Gershoni-Baruch R, Harlan JM, Etzioni A. In vivo neutrophil and lymphocyte function studies in a patient with leukocyte adhesion deficiency type II. Blood. 1994 Sep 1;84(5):1635–1639. [PubMed]
  • von Andrian UH, Berger EM, Ramezani L, Chambers JD, Ochs HD, Harlan JM, Paulson JC, Etzioni A, Arfors KE. In vivo behavior of neutrophils from two patients with distinct inherited leukocyte adhesion deficiency syndromes. J Clin Invest. 1993 Jun;91(6):2893–2897. [PMC free article] [PubMed]
  • Watson ML, Kingsmore SF, Johnston GI, Siegelman MH, Le Beau MM, Lemons RS, Bora NS, Howard TA, Weissman IL, McEver RP, et al. Genomic organization of the selectin family of leukocyte adhesion molecules on human and mouse chromosome 1. J Exp Med. 1990 Jul 1;172(1):263–272. [PMC free article] [PubMed]
  • Mayadas TN, Johnson RC, Rayburn H, Hynes RO, Wagner DD. Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell. 1993 Aug 13;74(3):541–554. [PubMed]
  • Labow MA, Norton CR, Rumberger JM, Lombard-Gillooly KM, Shuster DJ, Hubbard J, Bertko R, Knaack PA, Terry RW, Harbison ML, et al. Characterization of E-selectin-deficient mice: demonstration of overlapping function of the endothelial selectins. Immunity. 1994 Nov;1(8):709–720. [PubMed]
  • Arbonés ML, Ord DC, Ley K, Ratech H, Maynard-Curry C, Otten G, Capon DJ, Tedder TF. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity. 1994 Jul;1(4):247–260. [PubMed]
  • Bullard DC, Qin L, Lorenzo I, Quinlin WM, Doyle NA, Bosse R, Vestweber D, Doerschuk CM, Beaudet AL. P-selectin/ICAM-1 double mutant mice: acute emigration of neutrophils into the peritoneum is completely absent but is normal into pulmonary alveoli. J Clin Invest. 1995 Apr;95(4):1782–1788. [PMC free article] [PubMed]
  • Ley K, Bullard DC, Arbonés ML, Bosse R, Vestweber D, Tedder TF, Beaudet AL. Sequential contribution of L- and P-selectin to leukocyte rolling in vivo. J Exp Med. 1995 Feb 1;181(2):669–675. [PMC free article] [PubMed]
  • Becker-André M, Hooft van Huijsduijnen R, Losberger C, Whelan J, Delamarter JF. Murine endothelial leukocyte-adhesion molecule 1 is a close structural and functional homologue of the human protein. Eur J Biochem. 1992 Jun 1;206(2):401–411. [PubMed]
  • Matzuk MM, Finegold MJ, Su JG, Hsueh AJ, Bradley A. Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature. 1992 Nov 26;360(6402):313–319. [PubMed]
  • Soriano P, Montgomery C, Geske R, Bradley A. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell. 1991 Feb 22;64(4):693–702. [PubMed]
  • Baez S. An open cremaster muscle preparation for the study of blood vessels by in vivo microscopy. Microvasc Res. 1973 May;5(3):384–394. [PubMed]
  • Ley K, Gaehtgens P. Endothelial, not hemodynamic, differences are responsible for preferential leukocyte rolling in rat mesenteric venules. Circ Res. 1991 Oct;69(4):1034–1041. [PubMed]
  • Kunkel EJ, Jung U, Bullard DC, Norman KE, Wolitzky BA, Vestweber D, Beaudet AL, Ley K. Absence of trauma-induced leukocyte rolling in mice deficient in both P-selectin and intercellular adhesion molecule 1. J Exp Med. 1996 Jan 1;183(1):57–65. [PMC free article] [PubMed]
  • Pries AR. A versatile video image analysis system for microcirculatory research. Int J Microcirc Clin Exp. 1988 Nov;7(4):327–345. [PubMed]
  • Kishimoto TK, Jutila MA, Berg EL, Butcher EC. Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science. 1989 Sep 15;245(4923):1238–1241. [PubMed]
  • Smith CW, Kishimoto TK, Abbassi O, Hughes B, Rothlein R, McIntire LV, Butcher E, Anderson DC, Abbass O. Chemotactic factors regulate lectin adhesion molecule 1 (LECAM-1)-dependent neutrophil adhesion to cytokine-stimulated endothelial cells in vitro. J Clin Invest. 1991 Feb;87(2):609–618. [PMC free article] [PubMed]
  • Phillips ML, Schwartz BR, Etzioni A, Bayer R, Ochs HD, Paulson JC, Harlan JM. Neutrophil adhesion in leukocyte adhesion deficiency syndrome type 2. J Clin Invest. 1995 Dec;96(6):2898–2906. [PMC free article] [PubMed]
  • Bosse R, Vestweber D. Only simultaneous blocking of the L- and P-selectin completely inhibits neutrophil migration into mouse peritoneum. Eur J Immunol. 1994 Dec;24(12):3019–3024. [PubMed]
  • Winn RK, Harlan JM. CD18-independent neutrophil and mononuclear leukocyte emigration into the peritoneum of rabbits. J Clin Invest. 1993 Sep;92(3):1168–1173. [PMC free article] [PubMed]
  • Tedder TF, Steeber DA, Pizcueta P. L-selectin-deficient mice have impaired leukocyte recruitment into inflammatory sites. J Exp Med. 1995 Jun 1;181(6):2259–2264. [PMC free article] [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...