Objective:The purpose of the current study was to determine if neutrophils infiltrate maternal systemic vascular tissue at the time of term labor.
Methods:Subcutaneous fat biopsies were obtained at cesarean delivery or abdominal surgery from laboring women (n = 5), non-laboring women (n = 5), and normal non-pregnant women (n = 5). Immunohistochemical staining was performed for CD66b, a neutrophil antigen, and intercellular adhesion molecule-1 (ICAM-1; CD54), an endothelial cell adhesion molecule for neutrophils. Vessels (10 to 2000 μm) were analyzed for intensity of staining and percentage of vessels with staining.
Results:CD66b staining intensity was significantly greater for laboring women at term than for non-laboring women at term or for normal non-pregnant women (1.3 ± 0.3 versus 0.2 ± 0.1 versus 0.2 ± 0.1, respectively, P <.01), Laboring women had significantly more vessels with staining for CD66b (79 ± 4 versus 24 ± 8 versus 19 ± 6%, P <.001), more vessels with neutrophils adhered and flattened to endothelium (67 ± 3 versus 16 ± 7 versus 12 ± 4%, P <.001), more vessels with neutrophils in the intima (30 ± 6 versus 5 ± 2 versus 2 ± 1%, P <.05), and a greater number of neutrophils per vessel (5.4 ± 1.1 versus 1.7 ± 0.5 versus 1.2 ± 0.3, P <.01) as compared to non-laboring or normal non-pregnant women. ICAM-1 staining was present in the endothelium of all groups, with no difference in staining intensity or percent of vessels stained. Between 86% to 96% of vessels stained for ICAM-1. Laboring patients had numerous leukocytes stained for ICAM-1 in their vessels.
Conclusion:This study demonstrates that neutrophils infiltrate maternal systemic vascular tissue at the time of term labor. Neutrophils were flattened and adhered to endothelium and infiltrated into the intimal space.
1. Romero R, Mazor M, Wu YK, et al. Infection in the pathogenesis of preterm labor. Semin Perinatol1988;12:262-279.
2.
2. Romero R, Erez O, Espinoza J. Intrauterine infection, preterm labor, and cytokines. J Soc Gynecol Investig2005;12:463-465.
3.
3. Veenstra van Neiuwenhoven AL, Bouman A, Moes H, et al. Cytokine production in natural killer cells and lymphocytes in pregnant women compared with women in the follicular phase of the ovarian cycle. Fertil Steril2002;77:1032-1037.
4.
4. Cunningham FG, Gant NF, Leveno KJ, Gilstrap LC, III, Hauth JC, Wenstrom KD. Williams obstetrics. New York: McGraw-Hill, 2001.
5.
5. Ledingham MA, Thomson AJ, Jordan F, Young A, Crawford M, Norman JE. Cell adhesion molecule expression in the cervix and myometrium during pregnancy and parturition. Obstet Gynecol2001;97:235-242.
6.
6. Thomson AJ, Telfer JF, Young A, et al. Leukocytes infiltrate the myometrium during human parturition: Further evidence that labour is an inflammatory process. Hum Reprod1999;14:229-236.
7.
7. Winkler M, Fisher DC, Ruck P, et al. Parturition at term: Parallel increases in interleukin-8 and proteinase concentrations and neutrophil count in the lower uterine segment. Hum Reprod1999;14:1096-1100.
8.
8. Hebisch G, Grauaug AA, Neumaier-Wagner PM, Stallmach T, Huch A, Huch R. The relationship between cervical dilatation, interleukin-6 and interleukin-8 during term labor. Acta Obstet Gynecol Scand2001;80:840-848.
9.
9. Leik CE, Walsh SW. Neutrophils infiltrate resistance-sized vessels of subcutaneous fat in women with preeclampsia. Hypertension2004;44:72-77.
10.
10. Skubitz KM, Campbell KD, Skubitz AP. Synthetic peptides of CD66a stimulate neutrophil adhesion to endothelial cells. J Immunol2000;164:4257-4264.
11.
11. Kuroki M, Matsuo Y, Kinugasa T, Matsuoka Y. Augmented expression and release of nonspecific cross-reacting antigens (NCAs), members of the CEA family, by human neutrophils during cell activation. J Leukoc Biol1992;52:551-557.
12.
12. Roebuck KA, Finnegan A. Regulation of intercellular adhesion molecule-1 (CD54) gene expression. J Leukoc Biol1999;66:876-888.
13.
13. Hebisch G, Neumaier-Wagner PM, Hugh R, von Mandach U. Maternal serum interleukin-1 beta, -6 and -8 levels and potential determinants in pregnancy and peripartum. J Perinat Med2004;32:475-480.
14.
14. Delgado I, Neubert R, Dudenhausen JW. Changes in white blood cells during parturition in mothers and newborn. Gynecol Obstet Invest1994;38:227-235.
15.
15. Hartmann KE, Barrett KE, Reid VC, McMahon MJ, Miller WC. Clinical usefulness of white blood cell count after cesarean delivery. Obstet Gynecol2000;96:295-300.
16.
16. Gervasi MT, Chaiworapongsa T, Naccasha N, et al. Phenotypic and metabolic characteristics of maternal monocytes and granulocytes in preterm labor with intact membranes. Am J Obstet Gynecol2001;185:1124-1129.
17.
17. Luppi P, Irwin TE, Simhan H, Deloia JA. CD11b Expression on circulating leukocytes increases in preparation for parturition. Am J Reprod Immunol2004;52:323-329.
18.
18. Molloy EJ, O'Neill AJ, Grantham JJ, et al. Labor induces a maternal inflammatory response syndrome. Am J Obstet Gynecol2004;190:448-455.
19.
19. Stanford SJ, Pepper JR, Burke-Gaffney A, Mitchell JA. Cytokine-activated human vascular smooth muscle delays apoptosis of neutrophils: Relevance of interactions between cyclo-oxygenase-2 and colony-stimulating factors. FASEB J2001;15:1813-1815.
20.
20. Isada NB, Grossman JH III. Perinatal infections. In: Gabbe SG, Niebyl JR, Simpson JL, eds. Obstetrics normal and problem pregnancies. New York: Churchhill Livingstone, 1991:1223-1299.
