Annexin A1, A2 and cytokine levels during experimental sepsis in calves

Document Type : Research Articles


1 University of Tehran

2 Research & Production Complex, Pasteur Institute of Iran, Tehran, Iran

3 University of tehran


Annexins are fundamentally related proteins that process a variety of physiologic and pathologic procedures, including suppression of inflammation. Ten Holstein-Frisian bull calves (10 ± 1 days old) weighting 50 ± 5 kg were chosen to induce the experimental septicaemia using O111:H8 strain of E. coli. Blood samples were collected to determine the plasma annexin A1 , annexin A2, TNF-α, IFN- γ, IL-8 and neutrophil count at 0, 24, 48, 72, 96 and 120 hours after induction of septicemia. Significant increased concentrations of serum annexin A1 and annexin A2 in circulating blood in response to experimental coliseptisemia were observed during experiment. Maximum levels of annexinA1 and A2 were recorded at 72h after challenge. A statistically significant increase in
blood neutrophil count occurred from beginning of septicemia untill 24h after onset of septicemia. Annexin A2 and Annexin A1 had no significant correlation with neutrophil count. Serum cytokine concentrations reached their maximum level at 48h after challenge and then decreased to basal level before antibiotic therapy. This study showed that serum annexin concentrations, increasing during colisepticemia in calves, in association with cytokines could be a reliable marker to confirm the occurrence of anti-inflammatory response.


Main Subjects

Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. The New England Journal of Medicine.
De Freitas I, Fernandez-Somoza M, Essenfeld-Sekler E, Cardier JE .Serum levels of the apoptosis-associated molecules, tumor necrosis factor-alpha/tumor necrosis factor type-I receptor and Fas/FasL in sepsis. Chest .2004; 125: 2238-2246.
Horlacher T, Noti C, de Paz JL, Bindschädler P, Hecht ML, Smith DF, Fukuda MN, Seeberger PH. Characterization of Annexin a1 glycan binding reveals binding to highly sulfated glycans with preference for highly sulfated heparan sulfate and heparin. Biochemistry .2011;50: 2650–2659.
Katoh N. Detection of Annexins I and IV in bronchoalveolar lavage fluids from calves inoculated with bovine herpes virus-1. Journal of Veterinary Medical Science 2000; 62: 37–41.
Canetti C, Silva J, Ferreira SH, Cunha FQ. Tumor necrosis factor-α and leukotriene B[4] mediate the neutrophil migration in immune inflammation. British Journal of Pharmacology .2001; 134:1619-1628.
DePablo R, Monserrat J, Reyes E, Diaz MD, Rodriguez ZM, Carballo F, De la HA, Prieto A, Alvarez-Mon M..Mortality in patients with septic shock correlates with anti-inflammatory but not proinflammatory immunomodulatory molecules. Journal of Intensive Care Medicine.2011; 26:125-132.
Perretti M, Gavins FN. Annexin 1: an endogenous anti-inflammatory protein. News in physiological sciences. 2003; 18: 60-64.
Tsai WH, Li IT, Yu YB, Hsu HC, Shih CH. Serial changes in plasma Annexin a1 and cortisol levels in sepsis patients. Chinese Journal of Physiology.2014; 57: 1-7.
Pupjalis D, Goetsch J, Kottas DJ, Volker G, Ursula R. Annexin A1 released from apoptotic cells acts through formyl peptide receptors to dampen inflammatory monocyte activation via JAK/STAT/ SOCS signalling. EMBO Molecular Medicine .2011; 3:102-114.
Luo M, Hajjar KA. Annexin A2 System in Human Biology: Cell Surface and Beyond. Seminars in Thrombosis and Hemostasis .2013; 39:338-346.
Ji NY, Park MY, Kang YH, Lee CI, Kim DG, Yeom YI, Jang YJ, Myung PK, Kim JW, Lee G, Kim JW, Lee K, Song EY. Evaluation of Annexin II as a potential serum marker for hepatocellular carcinoma using a developed sandwich ELISA method. International Journal of Molecular Medicine. 2009; 24:765-771.
Walther A, Riehemann K , Gerke V. A novel ligand of the formyl peptide receptor: Annexin I regulates neutrophil extravasation by interacting with the FPR. Molecular Cell .2000; 5: 831-840.
Acquisto FD, Perretti M, Flower RJ. Annexin-A1: a pivotal regulator of the innate and adaptive immune systems. British Journal of Pharmacology .2008; 155: 152–169.
Hulbert, L.E., Cobb, C.J., Carroll, J.A. and Bullous, M.A.[2011] Effects of changing feeding milk replacer from twice to once daily on Holstein calf innate immune responses before and after weaning. The Journal of Dairy Science 94, 2557-2565.
Mokhber Dezfouli MR. Cow calf health and diseases. 1st ed., 2007.University of Tehran Press, Tehran, Iran.
Mohri M, Poorkabir M A, Hassani Tabatabai AM, Mokhber Dezfuli MR. Seasonal variation of serum total protein and gammaglobulin level of neonatal calves in a dairy farm of Tehran suburb. Journal of Veterinary Research. . 1999; 54: 25-30.
Lotfollahzadeh S, Mokhber Dezfouli MR, Khazraei Nia P,Tajik P. Evaluation of influence of two methods of artificially feeding colostrum on serum gammaglobulin concentrations of neonatal calves. Journal of Veterinary Research.2003; 58: 79-82.