Pregnancy Enzymes and Placental Polymorphism: I. Alkaline Phosphatase

Placental alkaline phosphatase (PLAP) in humans shows a high degree of genetic polymorphism as disclosed by electrophoretic analysis. Human testes contain trace amounts of a PLAP-like enzyme, that although immunologically cross-reactive with PLAP, shows unique catalytic properties.As an alternative approach to study enzyme polymorphism we have developed monoclonal antibodies to purified allelic variants of PLAP. Five different monoclonal antibodies are described in this report. The antibodies react with different epitopes on the PLAP molecule. Both conformational dependent and independent determinants are detected. Two epitopes are modified when comparing the S and F allelic variants of PLAP. One epitope is common to PLAP and the intestinal isoenzyme of alkaline phosphatase. The five epitopes appear to be mapped on two rather distant antigenic domains. Combinations of any two antibodies binding to different domains give immunoprecipitates with PLAP on Ouchterlony tests and give good response in sandwich enzyme-linked immunosorbent assays.A study of PLAP-like enzyme in 32 individual testis samples indicates differences in four of the epitopes when compared with PLAP. Four types of testicular enzymes can be distinguished based on their reactivities. These results indicate structural differences between the testicular PLAP-like enzyme and PLAP. These differences are compatible with an underlying genetic mechanism.Alkaline phosphatases in humans are encoded by at least three different structural gene loci. One codes for the tissue unspecific alkaline phosphatase (liver-bone-kidney type), at least one for the intestinal alkaline phosphatase and at least one for PLAP [1,2]. These three isoenzymes show quite different peptide maps on two-dimensional gels [2,3], and can be distinguished from each other immunochemically and on catalytic grounds [4 -61 (for review see [7,8]). PLAP and the intestinal alkaline phosphatase seem to be more closely related to each other than to the tissue unspecific enzyme. They are cross-reactive with polyclonal antibodies against either of them. PLAP is particularly interesting, since it is a rather late evolutionary gene product, detectable only in orangutan, chimpanzee and human placentae [9, lo]. It displays a high degree of genetic polymorphism. Three common and more than 15 rare allelic variants have been described by use of electrophoresis on starch gels [l I]. PLAP is a dimeric enzyme, composed of subunits of approximately 65 kDa. The three common alleles Pis, PIF and PI' (new nomenclature PI', PI2 and PI3) give rise to six homozygous and heterozygous phenotypes S, FS, F, SI, FI, I (new nomenclature l, 2-1,2,3-1,3-2,3)that comprise approximately 98 % of all the placental variants.The structural difference between these allelic variants has as yet not been elucidated.Further interest in the placental enzyme stems from the demonstration that PLAP and PLAP-like enzymes are proAbbreviations. PLAP, placental alkaline phosphatase; ELISA, enzyme-linked immunosorbent assay; HRP, horse-radish ...

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“…Fresh placentae were collected at delivery, individually homogenized and typed by electrophoresis as described [19].…”

Section: Placental Alkaline Phosphatasementioning

confidence: 99%

Antigenic determinants of human placental and testicular placental‐like alkaline phosphatases as mapped by monoclonal antibodies

Millán

Stigbrand

1983

European Journal of Biochemistry

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“…Three common alleles (ALPp, ALPp and ALPp) and a large number of rare al leles have been demonstrated by electro phoresis [1][2][3]. Additional genetic varia tion has been revealed by immunochemi cal techniques [4,5].…”

Section: Introductionmentioning

confidence: 99%

Correlation between Rsal Restriction Fragment Length Polymorphism and Electrophoretic Types of Human Placental Alkaline Phosphatase

Beckman

Lundgren

et al. 1989

Hum Hered

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Restriction fragment length polymorphism (RFLP) of human alkaline phosphatases was studied in a population sample from northern Sweden using a placental alkaline phosphatase (PLAP) cDNA probe. After digestion of human genomic DNA with Rsal the Southern blots showed DNA fragments most probably derived from three genes: PLAP, germ cell alkaline phosphatase (PLAP-like) and intestinal alkaline phosphatase. In agreement with a previous study, a two-allele polymorphism was found in PLAP with bands at 1.6 kilobases (A1) and 1.8 kilobases (A2). The gene frequencies of A1 and A2 were 0.46 and 0.54, respectively. There was a significant correlation between the Rsal RFLPs and electrophoretic types of PLAP; RSAI A2 showed an association with the ALP²_Pallele of PLAP.

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“…One of the earliest studies by Beckman et al [1966] did not find any correlation of PLAP type either with sex, birth order or birth weight of the newborn or ABO and Rh type of mother. However, the length of gestation was found to be lowest in type B, intermediate in type AB and highest in type A [terminology of Boyer, 1961].…”

Section: Introductionmentioning

confidence: 86%

Relationship between Placental Alkaline Phosphatase Types and Obstetric History of Mother

Balgir¹

1988

Hum Hered

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Pregnancy Enzymes and Placental Polymorphism: I. Alkaline Phosphatase

Cited by 27 publications

References 2 publications

Antigenic determinants of human placental and testicular placental‐like alkaline phosphatases as mapped by monoclonal antibodies

Antigenic determinants of human placental and testicular placental‐like alkaline phosphatases as mapped by monoclonal antibodies

Correlation between Rsal Restriction Fragment Length Polymorphism and Electrophoretic Types of Human Placental Alkaline Phosphatase

Relationship between Placental Alkaline Phosphatase Types and Obstetric History of Mother

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