A role for Rab27 in neutrophil chemotaxis and lung recruitment

BMC Cell Biology

Miguel C Seabra¹  Alistair N Hume²  Sara M Rankin⁴  Mark A Birrell³  Rebecca C Furze⁴  Rajesh K Singh⁵ 

[1] Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, UK;School of Biomedical Sciences, University of Nottingham, Nottingham, UK;Respiratory Pharmacology, National Heart and Lung Institute, Imperial College London, London, UK;Leukocyte Biology, National Heart and Lung Institute, Imperial College London, London, UK;Weill Cornell Medical College, 1300 York Avenue, New York 10065, NY, USA

关键词: Exocytosis;    Chemotaxis;    Neutrophil;    Rab27;   

Others  :  1088719
DOI  :  10.1186/s12860-014-0039-z

 received in 2014-07-16, accepted in 2014-10-16,  发布年份 2014

【 摘 要 】

Background

Neutrophils are a critical part of the innate immune system. Their ability to migrate into infected or injured tissues precedes their role in microbial killing and clearance. We have previously shown that Rab27a can promote neutrophil migration by facilitating uropod release through protease secretion from primary granule exocytosis at the cell rear. Rab27b has been implicated in primary granule exocytosis but its role in neutrophil migration has not been investigated.

Results

Here we found Rab27b to be expressed in bone marrow derived neutrophils and Rab27b knockout (Rab27b KO) along with Rab27a/b double knockout (Rab27DKO) neutrophils exhibited impaired transwell migration in vitro in response to chemokines MIP-2 and LTB₄. Interestingly, no additional defect in migration was observed in Rab27DKO neutrophils compared with Rab27b KO neutrophils. In vivo, Rab27DKO mice displayed severe impairment in neutrophil recruitment to the lungs in a MIP-2 dependent model but not in an LPS dependent model.

Conclusions

These data taken together implicate Rab27b in the regulation of neutrophil chemotaxis, likely through the regulation of primary granule exocytosis.

【 授权许可】

   
2014 Singh et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Nathan C: Neutrophils and immunity: challenges and opportunities. Nat Rev Immun 2006, 6:173-182.
• [2]Hager M, Cowland JB, Borregaard N: Neutrophil granules in health and disease. J Intern Med 2010, 268:25-34.
• [3]Furze RC, Rankin SM: Neutrophil mobilization and clearance in the bone marrow. Immunology 2008, 125:281-288.
• [4]Lauffenburger DA, Horwitz AF: Cell migration: a physically integrated molecular process. Cell 1996, 84:359-369.
• [5]Lawson CD, Donald S, Anderson KE, Patton DT, Welch HC: P-Rex1 and Vav1 cooperate in the regulation of formyl-methionyl-leucyl-phenylalanine-dependent neutrophil responses. J Immunol 2011, 186:1467-1476.
• [6]Roberts AW, Kim C, Zhen L, Lowe JB, Kapur R, Petryniak B, Spaetti A, Pollock JD, Borneo JB, Bradford GB, Atkinson SJ, Dinauer MC, Williams DA: Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. Immunity 1999, 10:183-196.
• [7]Szczur K, Zheng Y, Filippi MD: The small Rho GTPase Cdc42 regulates neutrophil polarity via CD11b integrin signaling. Blood 2009, 114:4527-4537.
• [8]Lawson MA, Maxfield FR: Ca(2+)- and calcineurin-dependent recycling of an integrin to the front of migrating neutrophils. Nature 1995, 377:75-79.
• [9]Alblas J, Ulfman L, Hordijk P, Koenderman L: Activation of Rhoa and ROCK are essential for detachment of migrating leukocytes. Mol Biol Cell 2001, 12:2137-2145.
• [10]Yoshinaga-Ohara N, Takahashi A, Uchiyama T, Sasada M: Spatiotemporal regulation of moesin phosphorylation and rear release by Rho and serine/threonine phosphatase during neutrophil migration. Exp Cell Res 2002, 278:112-122.
• [11]Morin NA, Oakes PW, Hyun YM, Lee D, Chin YE, King MR, Springer TA, Shimaoka M, Tang JX, Reichner JS, Kim M: Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration. J Exp Med 2008, 205:195-205.
• [12]Lokuta MA, Senetar MA, Bennin DA, Nuzzi PA, Chan KT, Ott VL, Huttenlocher A: Type Igamma PIP kinase is a novel uropod component that regulates rear retraction during neutrophil chemotaxis. Mol Biol Cell 2007, 18:5069-5080.
• [13]Colvin RA, Means TK, Diefenbach TJ, Moita LF, Friday RP, Sever S, Campanella GS, Abrazinski T, Manice LA, Moita C, Andrews NW, Wu D, Hacohen N, Luster AD: Synaptotagmin-mediated vesicle fusion regulates cell migration. Nat Immunol 2010, 11:495-502.
• [14]Singh RK, Liao W, Tracey-White D, Recchi C, Tolmachova T, Rankin SM, Hume AN, Seabra MC: Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment. J Cell Sci 2012, 125:1652-1656.
• [15]Stinchcombe JC, Barral DC, Mules EH, Booth S, Hume AN, Machesky LM, Seabra MC, Griffiths GM: Rab27a is required for regulated secretion in cytotoxic T lymphocytes. J Cell Biol 2001, 152:825-834.
• [16]Haddad EK, Wu X, Hammer JA 3rd, Henkart PA: Defective granule exocytosis in Rab27a-deficient lymphocytes from Ashen mice. J Cell Biol 2001, 152:835-842.
• [17]Munafo DB, Johnson JL, Ellis BA, Rutschmann S, Beutler B, Catz SD: Rab27a is a key component of the secretory machinery of azurophilic granules in granulocytes. Biochem J 2007, 402:229-239.
• [18]Wood SM, Meeths M, Chiang SC, Bechensteen AG, Boelens JJ, Heilmann C, Horiuchi H, Rosthoj S, Rutynowska O, Winiarski J, Stow JL, Nordenskjold M, Henter JI, Ljunggren HG, Bryceson YT: Different NK cell-activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity. Blood 2009, 114:4117-4127.
• [19]Mizuno K, Tolmachova T, Ushakov DS, Romao M, Abrink M, Ferenczi MA, Raposo G, Seabra MC: Rab27b regulates mast cell granule dynamics and secretion. Traffic 2007, 8:883-892.
• [20]Singh RK, Mizuno K, Wasmeier C, Wavre-Shapton ST, Recchi C, Catz SD, Futter C, Tolmachova T, Hume AN, Seabra MC: Distinct and opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cell secretion. FEBS J 2013, 280:892-903.
• [21]Tolmachova T, Abrink M, Futter CE, Authi KS, Seabra MC: Rab27b regulates number and secretion of platelet dense granules. Proc Natl Acad Sci U S A 2007, 104:5872-5877.
• [22]Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C: Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 2010, 12:19-30. sup pp 1–13
• [23]Johnson JL, Brzezinska AA, Tolmachova T, Munafo DB, Ellis BA, Seabra MC, Hong H, Catz SD: Rab27a and Rab27b regulate neutrophil azurophilic granule exocytosis and NADPH oxidase activity by independent mechanisms. Traffic 2010, 11:533-547.
• [24]Hume AN, Ushakov DS, Tarafder AK, Ferenczi MA, Seabra MC: Rab27a and MyoVa are the primary Mlph interactors regulating melanosome transport in melanocytes. J Cell Sci 2007, 120:3111-3122.
• [25]Elstak ED, Neeft M, Nehme NT, Voortman J, Cheung M, Goodarzifard M, Gerritsen HC, van Bergen En Henegouwen PM, Callebaut I, de Saint Basile G, van der Sluijs P: The munc13-4-rab27 complex is specifically required for tethering secretory lysosomes at the plasma membrane. Blood 2011, 118:1570-1578.
• [26]Barral DC, Ramalho JS, Anders R, Hume AN, Knapton HJ, Tolmachova T, Collinson LM, Goulding D, Authi KS, Seabra MC: Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome. J Clin Investig 2002, 110:247-257.
• [27]Tanaka C, Kaji H, He J, Hazama R, Yokoyama K, Kinoshita E, Tsujioka T, Tohyama K, Yamamura H, Nishio H, Tohyama Y: Rab27b regulates c-kit expression by controlling the secretion of stem cell factor. Biochem Biophys Res Commun 2012, 419:368-373.
• [28]Johnson JL, Hong H, Monfregola J, Catz SD: Increased survival and reduced neutrophil infiltration of the liver in Rab27a- but not Munc13-4-deficient mice in lipopolysaccharide-induced systemic inflammation. Infect Immun 2011, 79:3607-3618.
• [29]Zarbock A, Allegretti M, Ley K: Therapeutic inhibition of CXCR2 by Reparixin attenuates acute lung injury in mice. Br J Pharmacol 2008, 155:357-364.
• [30]Reutershan J, Morris MA, Burcin TL, Smith DF, Chang D, Saprito MS, Ley K: Critical role of endothelial CXCR2 in LPS-induced neutrophil migration into the lung. J Clin Investig 2006, 116:695-702.
• [31]Chapman RW, Minnicozzi M, Celly CS, Phillips JE, Kung TT, Hipkin RW, Fan X, Rindgen D, Deno G, Bond R, Gonsiorek W, Billah MM, Fine JS, Hey JA: A novel, orally active CXCR1/2 receptor antagonist, Sch527123, inhibits neutrophil recruitment, mucus production, and goblet cell hyperplasia in animal models of pulmonary inflammation. J Pharmacol Exp Ther 2007, 322:486-493.
• [32]Nightingale TD, Pattni K, Hume AN, Seabra MC, Cutler DF: Rab27a and MyRIP regulate the amount and multimeric state of VWF released from endothelial cells. Blood 2009, 113:5010-5018.
• [33]Mizgerd JP, Kubo H, Kutkoski GJ, Bhagwan SD, Scharffetter-Kochanek K, Beaudet AL, Doerschuk CM: Neutrophil emigration in the skin, lungs, and peritoneum: different requirements for CD11/CD18 revealed by CD18-deficient mice. J Exp Med 1997, 186:1357-1364.
• [34]Fukuda M: Rab27 Effectors, Pleiotropic Regulators in Secretory Pathways. Traffic 2013, 14:949-963.
• [35]Zen K, Guo YL, Li LM, Bian Z, Zhang CY, Liu Y: Cleavage of the CD11b extracellular domain by the leukocyte serprocidins is critical for neutrophil detachment during chemotaxis. Blood 2011, 117:4885-4894.
• [36]Wengner AM, Pitchford SC, Furze RC, Rankin SM: The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation. Blood 2008, 111:42-49.
• [37]Brzezinska AA, Johnson JL, Munafo DB, Crozat K, Beutler B, Kiosses WB, Ellis BA, Catz SD: The Rab27a effectors JFC1/Slp1 and Munc13-4 regulate exocytosis of neutrophil granules. Traffic 2008, 9:2151-2164.
• [38]Fulton SA, Reba SM, Martin TD, Boom WH: Neutrophil-mediated mycobacteriocidal immunity in the lung during Mycobacterium bovis BCG infection in C57BL/6 mice. Infect Immun 2002, 70:5322-5327.
• [39]Birrell MA, Wong S, Dekkak A, De Alba J, Haj-Yahia S, Belvisi MG: Role of matrix metalloproteinases in the inflammatory response in human airway cell-based assays and in rodent models of airway disease. J Pharmacol Exp Ther 2006, 318:741-750.
• [40]Birrell MA, Wong S, Hele DJ, McCluskie K, Hardaker E, Belvisi MG: Steroid-resistant inflammation in a rat model of chronic obstructive pulmonary disease is associated with a lack of nuclear factor-kappaB pathway activation. Am J Respir Crit Care Med 2005, 172:74-84.