Pathways and Bottlenecks in the Web of Inflammatory Adhesion Molecules and Chemoattractants

Overview

Journal Immunol Res

Specialty Allergy & Immunology

Date 2001 Aug 4

PMID 11485212

Citations 9

Authors

K Ley

Affiliations

Soon will be listed here.

Abstract

Leukocyte recruitment requires capture, rolling, activation, adhesion, and transmigration. Adhesion molecules and chemoattractants have been identified that mediate each of these steps. Their functions often overlap, but the combined absence of some molecules can lead to severe spontaneous phenotypes, as seen in CD18-/- mice, or early lethality, as in CD18-/- E-selectin-/- mice. These groups of molecules define bottlenecks that restrict the inflammatory response. Adhesion molecules and activation mechanisms can also form groups of preferential usage, or pathways. Based on these findings, a web-like model may represent the inflammatory process better than the linear cascade model. Bottlenecks and pathways depend on the degree and nature of overlapping functions, the disease process, tissue site, and the inflammatory stimulus.

Citing Articles

Inflammation in cancer: therapeutic opportunities from new insights.

Xie Y, Liu F, Wu Y, Zhu Y, Jiang Y, Wu Q Mol Cancer. 2025; 24(1):51.

PMID: 39994787 PMC: 11849313. DOI: 10.1186/s12943-025-02243-8.

LFA-1 Mediates Cytotoxicity and Tissue Migration of Specific CD8 T Cells after Heterologous Prime-Boost Vaccination against Infection.

Ferreira C, Cariste L, Santos Virgilio F, Moraschi B, Monteiro C, Vieira Machado A Front Immunol. 2017; 8:1291.

PMID: 29081775 PMC: 5645645. DOI: 10.3389/fimmu.2017.01291.

The relationship between inflammatory markers, angiogenesis, and obesity.

Tahergorabi Z, Khazaei M ARYA Atheroscler. 2013; 9(4):247-53.

PMID: 23970920 PMC: 3746949.

Effects of symptomatic and asymptomatic isolates of Blastocystis hominis on colorectal cancer cell line, HCT116.

Chan K, Chandramathi S, Suresh K, Chua K, Kuppusamy U Parasitol Res. 2012; 110(6):2475-80.

PMID: 22278727 DOI: 10.1007/s00436-011-2788-3.

Adhesion molecule levels in serum and cerebrospinal fluid in children with bacterial meningitis and sepsis.

Jaber S, Hamed E, Hamed S J Pediatr Neurosci. 2011; 4(2):76-85.

PMID: 21887188 PMC: 3162794. DOI: 10.4103/1817-1745.57326.

References

van Eeden S, Bicknell S, Walker B, Hogg J . Polymorphonuclear leukocytes L-selectin expression decreases as they age in circulation. Am J Physiol. 1997; 272(1 Pt 2):H401-8. DOI: 10.1152/ajpheart.1997.272.1.H401. View

Robinson S, Frenette P, Rayburn H, Cummiskey M, Wagner D, Hynes R . Multiple, targeted deficiencies in selectins reveal a predominant role for P-selectin in leukocyte recruitment. Proc Natl Acad Sci U S A. 1999; 96(20):11452-7. PMC: 18054. DOI: 10.1073/pnas.96.20.11452. View

Foy D, Ley K . Intercellular adhesion molecule-1 is required for chemoattractant-induced leukocyte adhesion in resting, but not inflamed, venules in vivo. Microvasc Res. 2000; 60(3):249-60. DOI: 10.1006/mvre.2000.2272. View

Arfors K, Lundberg C, Lindbom L, Lundberg K, Beatty P, Harlan J . A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood. 1987; 69(1):338-40. View

Cacalano G, Lee J, Kikly K, Ryan A, Hultgren B, Wood W . Neutrophil and B cell expansion in mice that lack the murine IL-8 receptor homolog. Science. 1994; 265(5172):682-4. DOI: 10.1126/science.8036519. View

Smolen J, Petersen T, Koch C, OKeefe S, Hanlon W, Seo S . L-selectin signaling of neutrophil adhesion and degranulation involves p38 mitogen-activated protein kinase. J Biol Chem. 2000; 275(21):15876-84. DOI: 10.1074/jbc.M906232199. View

Jung U, Ley K . Mice lacking two or all three selectins demonstrate overlapping and distinct functions for each selectin. J Immunol. 1999; 162(11):6755-62. View

Forlow S, White E, Barlow S, Feldman S, Lu H, Bagby G . Severe inflammatory defect and reduced viability in CD18 and E-selectin double-mutant mice. J Clin Invest. 2000; 106(12):1457-66. PMC: 387256. DOI: 10.1172/JCI10555. View

Penn M, Dworkin M . Robert Koch and two visions of microbiology. Bacteriol Rev. 1976; 40(2):276-83. PMC: 413958. DOI: 10.1128/br.40.2.276-283.1976. View

10.

Gurtner G, Davis V, Li H, McCoy M, Sharpe A, Cybulsky M . Targeted disruption of the murine VCAM1 gene: essential role of VCAM-1 in chorioallantoic fusion and placentation. Genes Dev. 1995; 9(1):1-14. DOI: 10.1101/gad.9.1.1. View

11.

Labow M, Norton C, Rumberger J, Shuster D, Hubbard J, Bertko R . Characterization of E-selectin-deficient mice: demonstration of overlapping function of the endothelial selectins. Immunity. 1994; 1(8):709-20. DOI: 10.1016/1074-7613(94)90041-8. View

12.

Jung U, Ramos C, Bullard D, Ley K . Gene-targeted mice reveal importance of L-selectin-dependent rolling for neutrophil adhesion. Am J Physiol. 1998; 274(5):H1785-91. DOI: 10.1152/ajpheart.1998.274.5.H1785. View

13.

Etzioni A, Frydman M, Pollack S, Avidor I, Phillips M, Paulson J . Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency. N Engl J Med. 1992; 327(25):1789-92. DOI: 10.1056/NEJM199212173272505. View

14.

Harlan J . Leukocyte adhesion deficiency syndrome: insights into the molecular basis of leukocyte emigration. Clin Immunol Immunopathol. 1993; 67(3 Pt 2):S16-24. DOI: 10.1006/clin.1993.1079. View

15.

Becker D, Lowe J . Leukocyte adhesion deficiency type II. Biochim Biophys Acta. 1999; 1455(2-3):193-204. DOI: 10.1016/s0925-4439(99)00071-x. View

16.

Yang J, Hirata T, Croce K, Merrill-Skoloff G, Tchernychev B, Williams E . Targeted gene disruption demonstrates that P-selectin glycoprotein ligand 1 (PSGL-1) is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration. J Exp Med. 1999; 190(12):1769-82. PMC: 2195714. DOI: 10.1084/jem.190.12.1769. View

17.

Ley K, Tedder T . Leukocyte interactions with vascular endothelium. New insights into selectin-mediated attachment and rolling. J Immunol. 1995; 155(2):525-8. View

18.

Lawrence M, BAINTON D, Springer T . Neutrophil tethering to and rolling on E-selectin are separable by requirement for L-selectin. Immunity. 1994; 1(2):137-45. DOI: 10.1016/1074-7613(94)90107-4. View

19.

Simon S, Burns A, Taylor A, Gopalan P, Lynam E, Sklar L . L-selectin (CD62L) cross-linking signals neutrophil adhesive functions via the Mac-1 (CD11b/CD18) beta 2-integrin. J Immunol. 1995; 155(3):1502-14. View

20.

Arbones M, Ord D, Ley K, Ratech H, Otten G, Capon D . Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity. 1994; 1(4):247-60. DOI: 10.1016/1074-7613(94)90076-0. View