• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jul 18, 1995; 92(15): 7011–7015.

Leukocytes express connexin 43 after activation with lipopolysaccharide and appear to form gap junctions with endothelial cells after ischemia-reperfusion.


Levels and subcellular distribution of connexin 43 (Cx43), a gap junction protein, were studied in hamster leukocytes before and after activation with endotoxin (lipopolysaccharide, LPS) both in vitro and in vivo. Untreated leukocytes did not express Cx43. However, Cx43 was clearly detectable by indirect immunofluorescence in cells treated in vitro with LPS (1 micrograms/ml, 3 hr). Cx43 was also detected in leukocytes obtained from the peritoneal cavity 5-7 days after LPS-induced inflammation. In some leukocytes that formed clusters Cx43 immunoreactivity was present at appositional membranes, suggesting formation of homotypic gap junctions. In cell homogenates of activated peritoneal macrophages, Cx43, detected by Western blot analysis, was mostly unphosphorylated. A second in vivo inflammatory condition studied was that induced by ischemia-reperfusion of the hamster cheek pouch. In this system, leukocytes that adhered to venular endothelial cells after 1 hr of ischemia, followed by 1 hr of reperfusion, expressed Cx43. Electron microscope observations revealed small close appositions, putative gap junctions, at leukocyte-endothelial cell and leukocyte-leukocyte contacts. These results indicate that the expression of Cx43 can be induced in leukocytes during an inflammatory response which might allow for heterotypic or homotypic intercellular gap junctional communication. Gap junctions may play a role in leukocyte extravasation.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Carlos TM, Harlan JM. Membrane proteins involved in phagocyte adherence to endothelium. Immunol Rev. 1990 Apr;114:5–28. [PubMed]
  • Butcher EC. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. [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]
  • Bevilacqua MP, Pober JS, Mendrick DL, Cotran RS, Gimbrone MA., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. [PMC free article] [PubMed]
  • Geng JG, Bevilacqua MP, Moore KL, McIntyre TM, Prescott SM, Kim JM, Bliss GA, Zimmerman GA, McEver RP. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature. 1990 Feb 22;343(6260):757–760. [PubMed]
  • Albelda SM, Buck CA. Integrins and other cell adhesion molecules. FASEB J. 1990 Aug;4(11):2868–2880. [PubMed]
  • Keane RW, Mehta PP, Rose B, Honig LS, Loewenstein WR, Rutishauser U. Neural differentiation, NCAM-mediated adhesion, and gap junctional communication in neuroectoderm. A study in vitro. J Cell Biol. 1988 Apr;106(4):1307–1319. [PMC free article] [PubMed]
  • Mege RM, Matsuzaki F, Gallin WJ, Goldberg JI, Cunningham BA, Edelman GM. Construction of epithelioid sheets by transfection of mouse sarcoma cells with cDNAs for chicken cell adhesion molecules. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7274–7278. [PMC free article] [PubMed]
  • Musil LS, Cunningham BA, Edelman GM, Goodenough DA. Differential phosphorylation of the gap junction protein connexin43 in junctional communication-competent and -deficient cell lines. J Cell Biol. 1990 Nov;111(5 Pt 1):2077–2088. [PMC free article] [PubMed]
  • Jongen WM, Fitzgerald DJ, Asamoto M, Piccoli C, Slaga TJ, Gros D, Takeichi M, Yamasaki H. Regulation of connexin 43-mediated gap junctional intercellular communication by Ca2+ in mouse epidermal cells is controlled by E-cadherin. J Cell Biol. 1991 Aug;114(3):545–555. [PMC free article] [PubMed]
  • Bennett MV, Barrio LC, Bargiello TA, Spray DC, Hertzberg E, Sáez JC. Gap junctions: new tools, new answers, new questions. Neuron. 1991 Mar;6(3):305–320. [PubMed]
  • Dermietzel R, Spray DC. Gap junctions in the brain: where, what type, how many and why? Trends Neurosci. 1993 May;16(5):186–192. [PubMed]
  • Hülser DF, Peters JH. Intercellular communication in phytohemagglutinin-induced lymphocyte agglutinates. Eur J Immunol. 1971 Dec;1(6):494–495. [PubMed]
  • Hülser DF, Peters JH. Contact cooperation in stimulated lymphocytes. II. Electrophysiological investigations on intercellular communication. Exp Cell Res. 1972 Oct;74(2):319–326. [PubMed]
  • Guinan EC, Smith BR, Davies PF, Pober JS. Cytoplasmic transfer between endothelium and lymphocytes: quantitation by flow cytometry. Am J Pathol. 1988 Sep;132(3):406–409. [PMC free article] [PubMed]
  • Beyer EC, Paul DL, Goodenough DA. Connexin family of gap junction proteins. J Membr Biol. 1990 Jul;116(3):187–194. [PubMed]
  • Willecke K, Hennemann H, Dahl E, Jungbluth S, Heynkes R. The diversity of connexin genes encoding gap junctional proteins. Eur J Cell Biol. 1991 Oct;56(1):1–7. [PubMed]
  • Bennett MV, Verselis VK. Biophysics of gap junctions. Semin Cell Biol. 1992 Feb;3(1):29–47. [PubMed]
  • Navab M, Liao F, Hough GP, Ross LA, Van Lenten BJ, Rajavashisth TB, Lusis AJ, Laks H, Drinkwater DC, Fogelman AM. Interaction of monocytes with cocultures of human aortic wall cells involves interleukins 1 and 6 with marked increases in connexin43 message. J Clin Invest. 1991 May;87(5):1763–1772. [PMC free article] [PubMed]
  • Beyer EC, Steinberg TH. Evidence that the gap junction protein connexin-43 is the ATP-induced pore of mouse macrophages. J Biol Chem. 1991 May 5;266(13):7971–7974. [PubMed]
  • Polacek D, Lal R, Volin MV, Davies PF. Gap junctional communication between vascular cells. Induction of connexin43 messenger RNA in macrophage foam cells of atherosclerotic lesions. Am J Pathol. 1993 Feb;142(2):593–606. [PMC free article] [PubMed]
  • Yamamoto T, Ochalski A, Hertzberg EL, Nagy JI. LM and EM immunolocalization of the gap junctional protein connexin 43 in rat brain. Brain Res. 1990 Feb 5;508(2):313–319. [PubMed]
  • Berthoud VM, Rook MB, Traub O, Hertzberg EL, Sáez JC. On the mechanisms of cell uncoupling induced by a tumor promoter phorbol ester in clone 9 cells, a rat liver epithelial cell line. Eur J Cell Biol. 1993 Dec;62(2):384–396. [PubMed]
  • Yasuhara H, Hobson RW, 2nd, Dillon PK, Durán WN. A new model for studying ischemia-reperfusion injury in hamster cheek pouch. Am J Physiol. 1991 Nov;261(5 Pt 2):H1626–H1629. [PubMed]
  • Borić MP, Donoso V, Fournier A, St Pierre S, Huidobro-Toro JP. Endothelin reduces microvascular blood flow by acting on arterioles and venules of the hamster cheek pouch. Eur J Pharmacol. 1990 Nov 6;190(1-2):123–133. [PubMed]
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Risley MS, Tan IP, Roy C, Sáez JC. Cell-, age- and stage-dependent distribution of connexin43 gap junctions in testes. J Cell Sci. 1992 Sep;103(Pt 1):81–96. [PubMed]
  • Levy JA, Weiss RM, Dirksen ER, Rosen MR. Possible communication between murine macrophages oriented in linear chains in tissue culture. Exp Cell Res. 1976 Dec;103(2):375–385. [PubMed]
  • Issekutz TB, Issekutz AC, Movat HZ. The in vivo quantitation and kinetics of monocyte migration into acute inflammatory tissue. Am J Pathol. 1981 Apr;103(1):47–55. [PMC free article] [PubMed]
  • Lasky LA. A 'roll' in acute inflammation. Curr Biol. 1993 Oct 1;3(10):680–682. [PubMed]
  • Granger DN, Benoit JN, Suzuki M, Grisham MB. Leukocyte adherence to venular endothelium during ischemia-reperfusion. Am J Physiol. 1989 Nov;257(5 Pt 1):G683–G688. [PubMed]
  • Lefer AM, Lefer DJ. Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock. Annu Rev Pharmacol Toxicol. 1993;33:71–90. [PubMed]
  • Reed KE, Westphale EM, Larson DM, Wang HZ, Veenstra RD, Beyer EC. Molecular cloning and functional expression of human connexin37, an endothelial cell gap junction protein. J Clin Invest. 1993 Mar;91(3):997–1004. [PMC free article] [PubMed]
  • Bruzzone R, Haefliger JA, Gimlich RL, Paul DL. Connexin40, a component of gap junctions in vascular endothelium, is restricted in its ability to interact with other connexins. Mol Biol Cell. 1993 Jan;4(1):7–20. [PMC free article] [PubMed]
  • Larson DM, Haudenschild CC, Beyer EC. Gap junction messenger RNA expression by vascular wall cells. Circ Res. 1990 Apr;66(4):1074–1080. [PubMed]
  • Zimmerman GA, Hill HR. Inflammatory mediators stimulate granulocyte adherence to cultured human endothelial cells. Thromb Res. 1984 Jul 15;35(2):203–217. [PubMed]
  • Grabstein KH, Urdal DL, Tushinski RJ, Mochizuki DY, Price VL, Cantrell MA, Gillis S, Conlon PJ. Induction of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor. Science. 1986 Apr 25;232(4749):506–508. [PubMed]
  • Aronson FR, Libby P, Brandon EP, Janicka MW, Mier JW. IL-2 rapidly induces natural killer cell adhesion to human endothelial cells. A potential mechanism for endothelial injury. J Immunol. 1988 Jul 1;141(1):158–163. [PubMed]
  • el-Sabban ME, Pauli BU. Cytoplasmic dye transfer between metastatic tumor cells and vascular endothelium. J Cell Biol. 1991 Dec;115(5):1375–1382. [PMC free article] [PubMed]
  • De Bruyn PP, Cho Y, Michelson S. Endothelial attachment and plasmalemmal apposition in the transcellular movement of intravascular leukemic cells entering the myeloid parenchyma. Am J Anat. 1989 Oct;186(2):115–126. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...